The effect of thyrotrophin-releasing hormone (TRH) on the circulating plasma levels of tri-iodoth... more The effect of thyrotrophin-releasing hormone (TRH) on the circulating plasma levels of tri-iodothyronine (T3) and thyroxine (T4) was determined in the same group of animals (four cattle and four Murrah buffaloes) during hot dry (HD), hot humid (HH) and cold environmental conditions. Plasma T3 and T4 concentrations were measured during 2 h before and up to 12 h after the administration of TRH (200 μg i.v.). In the preinjection period in both cattle and buffaloes T3 levels were significantly lower in HH conditions. No significant difference in basal (preinjection) T3 levels was observed during HD and cold seasons in cattle. The highest T3 levels were obtained in buffaloes during HD season with intermediate values during the cold months. Plasma T4 levels in these animals were reversed during HD and HH months. In both cattle and buffaloes there was a biphasic response of T3 and T4 to TRH treatment and this varied with time and in size. The season significantly affected the T3 response t...
Indian Journal of Endocrinology and Metabolism, 2004
... Among Adolscent And Young Women With Polycystic Ovary Syndrome In India Ganie M Ashraf, M. L ... more ... Among Adolscent And Young Women With Polycystic Ovary Syndrome In India Ganie M Ashraf, M. L Khurana, M Eunice, N Gupta, S. N ... was present in 42.8 % subjects and when correlated with OGTT abnormality, it showed no significant correlation, although a rising trend was ...
Master N had genital malformation at birth and had bilateral gonads in the labial fold. He was re... more Master N had genital malformation at birth and had bilateral gonads in the labial fold. He was reared as a boy and corrective surgery was done at the age of 4 years and was reassessed at the age of 14 years. His testosterone/dihydrotestosterone (DHT) was 11.8 (reference range <=10). Molecular analysis of SRD5A2 gene indicated the presence of a novel heterozygous missense mutation of p.A52T in exon 1, which was also detected in mother. The father, sister and maternal grandfather were found to have normal SRD5A2 gene sequence. We also detected an intronic (1-2) homozygous T>C transition in patient, whereas both parents were found to have the same transition in heterozygous form. Although 5α-steroid reductase 2 deficiency is an autosomal-recessive disorder, in this case, it appears that there may be a dominant inheritance because only one identified mutation was present which was passed from mother to son.
T is converted to a more potent androgen, DHT by the action of microsomal membrane enzyme 5α redu... more T is converted to a more potent androgen, DHT by the action of microsomal membrane enzyme 5α reductase 2. Defects in 5α reductase 2 isozyme results in incomplete virilisation of external male genitalia. Mutations in SRD5A2 gene leads to diminished enzyme activity, thus hampering DHT synthesis from T. We describe two unrelated patients from India with 5αRD2 due to novel insertion of nucleotides in the exon 1 of SRD5A2 gene that lead to premature termination of protein. Master S (case 1; III.8) was 3 years old at initial evaluation, had perineoscrotal hypospadias, microphallus and both testes were palpable in the inguinal region. Master P (case 2; III.9) was born as normal full term baby. He had primary complaint of microphallus, penoscrotal hypospadias and gonads in the inguinal region. Diagnosis of 5αRD2 was made, as T/DHT ratio in the two cases was 41 and 131.2 respectively. Sequence analysis of SRD5A2 gene showed an insertion of nucleotides TA in exon 1 (c.188_189). This resulted in premature termination of the protein due to stop codon at amino acid position 7. The protein formed is drastically truncated and inadequate protein synthesized explains the phenotypic characteristics of our patients.
Androgen excess is believed to be one of the major factors responsible for poor fertility outcome... more Androgen excess is believed to be one of the major factors responsible for poor fertility outcomes in females with congenital adrenal hyperplasia (CAH). Some believe that the adverse effect of androgens on fertility could have its origins as early as the antenatal years. To assess the impact of prolonged androgen exposure on fertility in CAH patients, we compiled the data of females with CAH followed in our clinic during the last 25 years who were sexually active and had not been initiated on steroids until age 9 years. This was an observational case study on seven patients with classical CAH who fulfilled the inclusion criteria. The age at initiation of therapy in these females ranged from 9 years to 29 years. All patients had varying degrees of genital ambiguity. The most common presenting complaints were genital ambiguity, non-development of secondary sexual characteristics, hirsutism and primary amenorrhea. Genital surgery was performed in all patients at ages ranging from 12 to 29 years, except for one patient who underwent surgery at age 5 years without a diagnosis of CAH being made. Breast development ensued within 2 to 12 months and periods started in all patients within 2-24 months of steroid initiation. There were 13 pregnancies (seven normal vaginal deliveries, two spontaneous abortions and four pregnancies were medically terminated). Late initiation of steroid therapy did not affect fertility in our cohort of CAH women. Androgen excess in situations of subnormal cortisol may not adversely affect fertility in females with CAH.
Indian Journal of Endocrinology and Metabolism, 2011
The pathogenesis of type 1 diabetes mellitus (T1DM) requires a genetic predisposition to particul... more The pathogenesis of type 1 diabetes mellitus (T1DM) requires a genetic predisposition to particular environmental triggers that may activate mechanisms leading to progressive loss of pancreatic beta cells. The polygenic nature T1DM and the influence of nongenetically determined factors in its causation are supported by data from studies using animal models and also from human studies. [1] Among the various socioeconomic denominators, a tendency toward shorter education and more practical type of employment was seen among parents of diabetic children from Europe; however, a South Indian study found that higher rather than lower socioeconomic status had influenced the absolute incidence and early onset of T1DM. [2-4] Strong clustering of T1DM in young children is thought to be an indication of in utero exposure to infection or other environmental agents. [5] The precise impacts of migration on the incidence of T1DM still not clear. Some early reports showed a different childhood T1DM incidence in France (4.6/100,000/year) and Canada (8.2/100,000/year), suggesting that those moving from low-risk areas to a high-risk area tend to adopt the incidence rate of that community. [6] Similarly, the incidence among Asian communities living in Bradford, Yorkshire, UK, during 1978-1981 was 4 times lower than non-Asians. However, it rose steadily during the 1981-1990 period finally leading to similar incidence among the children of non-Asian parents and the first generation of Asian children born in the UK. [7] Studies conducted in various European countries have found a strong association of advanced maternal or paternal age at birth to the risk of A B S T R A C T Background: The pathogenesis of type 1 diabetes mellitus (T1DM) requires a genetic predisposition to particular environmental triggers that may activate mechanisms leading to progressive loss of pancreatic beta cells. Aims: We tried to compare the impact of some demographic and environmental factors and breast-feeding on children (aged < 18 years) with recent onset diabetes mellitus (≤1 year) with that on age, sex, and socioeconomic status-matched controls. Material and Methods: A total of 43 consecutive patients (male, 24, mean age ± SD = 12.58 ± 9.6 years) and equal number of controls without diabetes mellitus or dysglycemia were included in this hospital-based case-control study. Results and Conclusions: A distinct peak in the incidence noted in the early adolescence with segregation in the winter months. Our patients did not differ significantly from the controls with regard to birth order, mode of delivery, parental age, parental education, dietary practices, breast-feeding, and migration in the family. Growth characteristics and nutritional status were also similar. A population study with more power will be better equipped to answer such queries.
Purpose of Study Atrial and brain natriuretic peptides (ANP, BNP) are circulating hormones of car... more Purpose of Study Atrial and brain natriuretic peptides (ANP, BNP) are circulating hormones of cardiac origin that play an important role in regulating blood pressure (BP) and cardiovascular homeostasis. The aim of this study was to investigate the role of natriuretic peptides (NPs) and microRNAs (miRs) in the ANP-dependent downregulation of NPRA, guanylyl cyclase (GC) activity, and cGMP accumulation, utilizing recombinant and/or native endogenous receptors. Methods Human embryonic kidney-293 (HEK-293) cells expressing recombinant receptor and MA-10 cells harboring native endogenous NPRA were cultured and pretreated with 100 nM ANP and BNP to determine 125I-ANP binding to NPRA. Cells were pretreated with 1 μM A71915 (GC inhibitor) to determine the effect on GC activity and with KT-5823 (PKG inhibitor) to examine the involvement of PKG in the regulation of NPRA. To confirm the role of miR-128 and miR-195 in NPRA regulation, the recombinant HEK-293 cells were transfected with the corre...
Indian Journal of Endocrinology and Metabolism, 2015
Congenital adrenal hyperplasia (CAH) is one of the hereditary diseases with autosomal recessive i... more Congenital adrenal hyperplasia (CAH) is one of the hereditary diseases with autosomal recessive inheritance resulting from a deficiency of steroid 21-hydroxylase (21-OH). It
Aims Wolfram syndrome, also known as DIDMOAD, is a relatively rare inherited neurodegenerative di... more Aims Wolfram syndrome, also known as DIDMOAD, is a relatively rare inherited neurodegenerative disorder, first evident in childhood as an association of juvenile-onset diabetes mellitus and optic atrophy, followed by diabetes insipidus and deafness. The aim of the study was to examine the clinical profile of patients with DIDMOAD syndrome presenting to a tertiary care hospital in north India. Methods Clinical presentation of juvenile-onset diabetes mellitus fulfilling the diagnosis of Wolfram syndrome was studied using a prepared standardized form. Results Subjects with juvenile-onset non-autoimmune diabetes mellitus attending the diabetic clinic at a tertiary care centre in north India were followed for 10 years and a diagnosis of fully developed Wolfram syndrome was confirmed in seven individuals. The series consisted of five male and two female patients with a mean age of 17.5 AE 7.34 years. Two subjects had consanguinity and none had any other family member affected. Optic atrophy was present in all, sensorineural hearing loss in 4 ⁄ 7, central diabetes insipidus in 4 ⁄ 7 and nephrogenic diabetes insipidus in 2 ⁄ 7 subjects. The new associations found were: spastic myoclonus, short stature with pancreatic malabsorption, nephrogenic diabetes insipidus, cyanotic heart disease and choledocholithiasis with cholangitis. Genetic analysis revealed mutation in exon 8 of the WFS1 gene in all the cases studied. Conclusions The present clinical series of Wolfram syndrome reveals a varied clinical presentation of the syndrome and some new associations.
Background The changes in β-cell function in high-risk populations who are apparently in the norm... more Background The changes in β-cell function in high-risk populations who are apparently in the normal glucose tolerant stage are still under investigation for designing earlier prevention strategies. This study analyzes changes in β-cell function and insulin sensitivity across fasting and two-hour glucose categories spanning normal glucose tolerance (NGT) to impaired glucose tolerance (IGT), in offspring of subjects with type-2 diabetes mellitus (T2DM) compared to the controls without a known family history of T2DM. Methods Offspring of T2DM patients (cases) and individuals without a family history of T2DM (controls) were the subjects for this cross-sectional study. All participants underwent a 75 g oral glucose tolerance test and blood samples were collected for plasma glucose, insulin, C-peptide and proinsulin, at zero, 30, 60, and 120 minutes. Results A total of 358 cases (age 23.0 ± 10.8 years, 54% males) and 287 controls (age 28.4 ± 8.10 years, 65% males) were the subjects of this study. Cases and controls were divided into subgroups based on fasting and twohour glucose categories spanning NGT to IGT. Compared to the reference category of controls (< 80 mg/dL for fasting glucose and < 84 mg/dL for two-hour glucose), cases with IGT had ~60% decline in both β-cell compensation (as measured as disposition index {0-120}) and insulin sensitivity (as measured as whole-body insulin sensitivity index {0-120}); adjusted for age, gender, and body mass index. From lower to higher fasting and two-hour glucose categories, there was a continuous and significant decline in β-cell compensation in both cases and controls. Significant reduction in first-phase insulin secretion, as measured as insulinogenic (0-30) index, was only observed among two-hour glucose categories, not among the fasting glucose categories. In the transition from late NGT cases to IGT cases, there was a significant decline in βcell compensation, first-phase insulin secretion (more prominent than a decline in overall β-cell secretion) and the changes in whole-body insulin sensitivity were not statistically significant. Conclusions The decline in β-cell compensation was continuous and significant in offspring of subjects with type-2 diabetes and controls without a known family history of diabetes from early normal glucose tolerant ranges to impaired glucose tolerant ranges. Compared to the strictest glucose controlled category of controls, approximately 60% decline was observed in β-cell compensation and insulin sensitivity, in impaired glucose tolerant offspring of subjects with type-2 diabetes mellitus.
The effect of hypothyroidism induced m female rats on histone acetylation pattern m the neonatal ... more The effect of hypothyroidism induced m female rats on histone acetylation pattern m the neonatal rat brain was studied. It is likely that thyroid hormone regulates the acetylation of histones and thereby influence their interaction with DNA and modulates transcription. Propylthiouracil (PTU), administered to induce hypothyroidism, resulted in a significant reduction m the thyroid and brain weight of neonatal rats. The circulating thyroxine levels were undetectable in both 14 and 21 day old pups. The hypothyroid condition was further confirmed by low levels of T4 (94.31 ng/g brain tissue vs 1811.29 ng/g in controls and 144.67 ng/g vs 1087.72 ng/g in controls at 14 and 21 days, respectively) and T3 (42.19 ng/g brain tissue vs 879.97 ng/g in controls and 60.62 ng/g vs 766.68 ng/g in controls at 14 and 21 days, respectively) in the neonatal rat brain. Histone acetylation pattern was similar in treated and control groups m the 14 day old rats. PTU treatment, however, resulted in significant (p&lt;0.01) reduction in acetylation in the H3 fraction at 21 days whereas no such changes were recorded in other histone fractions. Lower histone acetylation in the 21 day old pups suggest a reduction m the transcriptional activity due to fewer initiation sites for RNA polymerase. It may be concluded that thyroid hormone may stimulate transcription of specific genes by increasing the acetylation of nucleosomal histones.
The effect of thyrotrophin-releasing hormone (TRH) on the circulating plasma levels of tri-iodoth... more The effect of thyrotrophin-releasing hormone (TRH) on the circulating plasma levels of tri-iodothyronine (T3) and thyroxine (T4) was determined in the same group of animals (four cattle and four Murrah buffaloes) during hot dry (HD), hot humid (HH) and cold environmental conditions. Plasma T3 and T4 concentrations were measured during 2 h before and up to 12 h after the administration of TRH (200 μg i.v.). In the preinjection period in both cattle and buffaloes T3 levels were significantly lower in HH conditions. No significant difference in basal (preinjection) T3 levels was observed during HD and cold seasons in cattle. The highest T3 levels were obtained in buffaloes during HD season with intermediate values during the cold months. Plasma T4 levels in these animals were reversed during HD and HH months. In both cattle and buffaloes there was a biphasic response of T3 and T4 to TRH treatment and this varied with time and in size. The season significantly affected the T3 response t...
Indian Journal of Endocrinology and Metabolism, 2004
... Among Adolscent And Young Women With Polycystic Ovary Syndrome In India Ganie M Ashraf, M. L ... more ... Among Adolscent And Young Women With Polycystic Ovary Syndrome In India Ganie M Ashraf, M. L Khurana, M Eunice, N Gupta, S. N ... was present in 42.8 % subjects and when correlated with OGTT abnormality, it showed no significant correlation, although a rising trend was ...
Master N had genital malformation at birth and had bilateral gonads in the labial fold. He was re... more Master N had genital malformation at birth and had bilateral gonads in the labial fold. He was reared as a boy and corrective surgery was done at the age of 4 years and was reassessed at the age of 14 years. His testosterone/dihydrotestosterone (DHT) was 11.8 (reference range <=10). Molecular analysis of SRD5A2 gene indicated the presence of a novel heterozygous missense mutation of p.A52T in exon 1, which was also detected in mother. The father, sister and maternal grandfather were found to have normal SRD5A2 gene sequence. We also detected an intronic (1-2) homozygous T>C transition in patient, whereas both parents were found to have the same transition in heterozygous form. Although 5α-steroid reductase 2 deficiency is an autosomal-recessive disorder, in this case, it appears that there may be a dominant inheritance because only one identified mutation was present which was passed from mother to son.
T is converted to a more potent androgen, DHT by the action of microsomal membrane enzyme 5α redu... more T is converted to a more potent androgen, DHT by the action of microsomal membrane enzyme 5α reductase 2. Defects in 5α reductase 2 isozyme results in incomplete virilisation of external male genitalia. Mutations in SRD5A2 gene leads to diminished enzyme activity, thus hampering DHT synthesis from T. We describe two unrelated patients from India with 5αRD2 due to novel insertion of nucleotides in the exon 1 of SRD5A2 gene that lead to premature termination of protein. Master S (case 1; III.8) was 3 years old at initial evaluation, had perineoscrotal hypospadias, microphallus and both testes were palpable in the inguinal region. Master P (case 2; III.9) was born as normal full term baby. He had primary complaint of microphallus, penoscrotal hypospadias and gonads in the inguinal region. Diagnosis of 5αRD2 was made, as T/DHT ratio in the two cases was 41 and 131.2 respectively. Sequence analysis of SRD5A2 gene showed an insertion of nucleotides TA in exon 1 (c.188_189). This resulted in premature termination of the protein due to stop codon at amino acid position 7. The protein formed is drastically truncated and inadequate protein synthesized explains the phenotypic characteristics of our patients.
Androgen excess is believed to be one of the major factors responsible for poor fertility outcome... more Androgen excess is believed to be one of the major factors responsible for poor fertility outcomes in females with congenital adrenal hyperplasia (CAH). Some believe that the adverse effect of androgens on fertility could have its origins as early as the antenatal years. To assess the impact of prolonged androgen exposure on fertility in CAH patients, we compiled the data of females with CAH followed in our clinic during the last 25 years who were sexually active and had not been initiated on steroids until age 9 years. This was an observational case study on seven patients with classical CAH who fulfilled the inclusion criteria. The age at initiation of therapy in these females ranged from 9 years to 29 years. All patients had varying degrees of genital ambiguity. The most common presenting complaints were genital ambiguity, non-development of secondary sexual characteristics, hirsutism and primary amenorrhea. Genital surgery was performed in all patients at ages ranging from 12 to 29 years, except for one patient who underwent surgery at age 5 years without a diagnosis of CAH being made. Breast development ensued within 2 to 12 months and periods started in all patients within 2-24 months of steroid initiation. There were 13 pregnancies (seven normal vaginal deliveries, two spontaneous abortions and four pregnancies were medically terminated). Late initiation of steroid therapy did not affect fertility in our cohort of CAH women. Androgen excess in situations of subnormal cortisol may not adversely affect fertility in females with CAH.
Indian Journal of Endocrinology and Metabolism, 2011
The pathogenesis of type 1 diabetes mellitus (T1DM) requires a genetic predisposition to particul... more The pathogenesis of type 1 diabetes mellitus (T1DM) requires a genetic predisposition to particular environmental triggers that may activate mechanisms leading to progressive loss of pancreatic beta cells. The polygenic nature T1DM and the influence of nongenetically determined factors in its causation are supported by data from studies using animal models and also from human studies. [1] Among the various socioeconomic denominators, a tendency toward shorter education and more practical type of employment was seen among parents of diabetic children from Europe; however, a South Indian study found that higher rather than lower socioeconomic status had influenced the absolute incidence and early onset of T1DM. [2-4] Strong clustering of T1DM in young children is thought to be an indication of in utero exposure to infection or other environmental agents. [5] The precise impacts of migration on the incidence of T1DM still not clear. Some early reports showed a different childhood T1DM incidence in France (4.6/100,000/year) and Canada (8.2/100,000/year), suggesting that those moving from low-risk areas to a high-risk area tend to adopt the incidence rate of that community. [6] Similarly, the incidence among Asian communities living in Bradford, Yorkshire, UK, during 1978-1981 was 4 times lower than non-Asians. However, it rose steadily during the 1981-1990 period finally leading to similar incidence among the children of non-Asian parents and the first generation of Asian children born in the UK. [7] Studies conducted in various European countries have found a strong association of advanced maternal or paternal age at birth to the risk of A B S T R A C T Background: The pathogenesis of type 1 diabetes mellitus (T1DM) requires a genetic predisposition to particular environmental triggers that may activate mechanisms leading to progressive loss of pancreatic beta cells. Aims: We tried to compare the impact of some demographic and environmental factors and breast-feeding on children (aged < 18 years) with recent onset diabetes mellitus (≤1 year) with that on age, sex, and socioeconomic status-matched controls. Material and Methods: A total of 43 consecutive patients (male, 24, mean age ± SD = 12.58 ± 9.6 years) and equal number of controls without diabetes mellitus or dysglycemia were included in this hospital-based case-control study. Results and Conclusions: A distinct peak in the incidence noted in the early adolescence with segregation in the winter months. Our patients did not differ significantly from the controls with regard to birth order, mode of delivery, parental age, parental education, dietary practices, breast-feeding, and migration in the family. Growth characteristics and nutritional status were also similar. A population study with more power will be better equipped to answer such queries.
Purpose of Study Atrial and brain natriuretic peptides (ANP, BNP) are circulating hormones of car... more Purpose of Study Atrial and brain natriuretic peptides (ANP, BNP) are circulating hormones of cardiac origin that play an important role in regulating blood pressure (BP) and cardiovascular homeostasis. The aim of this study was to investigate the role of natriuretic peptides (NPs) and microRNAs (miRs) in the ANP-dependent downregulation of NPRA, guanylyl cyclase (GC) activity, and cGMP accumulation, utilizing recombinant and/or native endogenous receptors. Methods Human embryonic kidney-293 (HEK-293) cells expressing recombinant receptor and MA-10 cells harboring native endogenous NPRA were cultured and pretreated with 100 nM ANP and BNP to determine 125I-ANP binding to NPRA. Cells were pretreated with 1 μM A71915 (GC inhibitor) to determine the effect on GC activity and with KT-5823 (PKG inhibitor) to examine the involvement of PKG in the regulation of NPRA. To confirm the role of miR-128 and miR-195 in NPRA regulation, the recombinant HEK-293 cells were transfected with the corre...
Indian Journal of Endocrinology and Metabolism, 2015
Congenital adrenal hyperplasia (CAH) is one of the hereditary diseases with autosomal recessive i... more Congenital adrenal hyperplasia (CAH) is one of the hereditary diseases with autosomal recessive inheritance resulting from a deficiency of steroid 21-hydroxylase (21-OH). It
Aims Wolfram syndrome, also known as DIDMOAD, is a relatively rare inherited neurodegenerative di... more Aims Wolfram syndrome, also known as DIDMOAD, is a relatively rare inherited neurodegenerative disorder, first evident in childhood as an association of juvenile-onset diabetes mellitus and optic atrophy, followed by diabetes insipidus and deafness. The aim of the study was to examine the clinical profile of patients with DIDMOAD syndrome presenting to a tertiary care hospital in north India. Methods Clinical presentation of juvenile-onset diabetes mellitus fulfilling the diagnosis of Wolfram syndrome was studied using a prepared standardized form. Results Subjects with juvenile-onset non-autoimmune diabetes mellitus attending the diabetic clinic at a tertiary care centre in north India were followed for 10 years and a diagnosis of fully developed Wolfram syndrome was confirmed in seven individuals. The series consisted of five male and two female patients with a mean age of 17.5 AE 7.34 years. Two subjects had consanguinity and none had any other family member affected. Optic atrophy was present in all, sensorineural hearing loss in 4 ⁄ 7, central diabetes insipidus in 4 ⁄ 7 and nephrogenic diabetes insipidus in 2 ⁄ 7 subjects. The new associations found were: spastic myoclonus, short stature with pancreatic malabsorption, nephrogenic diabetes insipidus, cyanotic heart disease and choledocholithiasis with cholangitis. Genetic analysis revealed mutation in exon 8 of the WFS1 gene in all the cases studied. Conclusions The present clinical series of Wolfram syndrome reveals a varied clinical presentation of the syndrome and some new associations.
Background The changes in β-cell function in high-risk populations who are apparently in the norm... more Background The changes in β-cell function in high-risk populations who are apparently in the normal glucose tolerant stage are still under investigation for designing earlier prevention strategies. This study analyzes changes in β-cell function and insulin sensitivity across fasting and two-hour glucose categories spanning normal glucose tolerance (NGT) to impaired glucose tolerance (IGT), in offspring of subjects with type-2 diabetes mellitus (T2DM) compared to the controls without a known family history of T2DM. Methods Offspring of T2DM patients (cases) and individuals without a family history of T2DM (controls) were the subjects for this cross-sectional study. All participants underwent a 75 g oral glucose tolerance test and blood samples were collected for plasma glucose, insulin, C-peptide and proinsulin, at zero, 30, 60, and 120 minutes. Results A total of 358 cases (age 23.0 ± 10.8 years, 54% males) and 287 controls (age 28.4 ± 8.10 years, 65% males) were the subjects of this study. Cases and controls were divided into subgroups based on fasting and twohour glucose categories spanning NGT to IGT. Compared to the reference category of controls (< 80 mg/dL for fasting glucose and < 84 mg/dL for two-hour glucose), cases with IGT had ~60% decline in both β-cell compensation (as measured as disposition index {0-120}) and insulin sensitivity (as measured as whole-body insulin sensitivity index {0-120}); adjusted for age, gender, and body mass index. From lower to higher fasting and two-hour glucose categories, there was a continuous and significant decline in β-cell compensation in both cases and controls. Significant reduction in first-phase insulin secretion, as measured as insulinogenic (0-30) index, was only observed among two-hour glucose categories, not among the fasting glucose categories. In the transition from late NGT cases to IGT cases, there was a significant decline in βcell compensation, first-phase insulin secretion (more prominent than a decline in overall β-cell secretion) and the changes in whole-body insulin sensitivity were not statistically significant. Conclusions The decline in β-cell compensation was continuous and significant in offspring of subjects with type-2 diabetes and controls without a known family history of diabetes from early normal glucose tolerant ranges to impaired glucose tolerant ranges. Compared to the strictest glucose controlled category of controls, approximately 60% decline was observed in β-cell compensation and insulin sensitivity, in impaired glucose tolerant offspring of subjects with type-2 diabetes mellitus.
The effect of hypothyroidism induced m female rats on histone acetylation pattern m the neonatal ... more The effect of hypothyroidism induced m female rats on histone acetylation pattern m the neonatal rat brain was studied. It is likely that thyroid hormone regulates the acetylation of histones and thereby influence their interaction with DNA and modulates transcription. Propylthiouracil (PTU), administered to induce hypothyroidism, resulted in a significant reduction m the thyroid and brain weight of neonatal rats. The circulating thyroxine levels were undetectable in both 14 and 21 day old pups. The hypothyroid condition was further confirmed by low levels of T4 (94.31 ng/g brain tissue vs 1811.29 ng/g in controls and 144.67 ng/g vs 1087.72 ng/g in controls at 14 and 21 days, respectively) and T3 (42.19 ng/g brain tissue vs 879.97 ng/g in controls and 60.62 ng/g vs 766.68 ng/g in controls at 14 and 21 days, respectively) in the neonatal rat brain. Histone acetylation pattern was similar in treated and control groups m the 14 day old rats. PTU treatment, however, resulted in significant (p&lt;0.01) reduction in acetylation in the H3 fraction at 21 days whereas no such changes were recorded in other histone fractions. Lower histone acetylation in the 21 day old pups suggest a reduction m the transcriptional activity due to fewer initiation sites for RNA polymerase. It may be concluded that thyroid hormone may stimulate transcription of specific genes by increasing the acetylation of nucleosomal histones.
Uploads
Papers by Madan Khurana