Maltese Canadian diabetes survey

Track 4. Basic Research s143 risk factors in newly detected diabetics were hypertension (63%) and obesity (56%). In comparison to nondiabetics whose percentage in the age group over 60 years was 47,9%, newly detected diabetics in this group represented 56,7%. Average age in non-diabetic group was 59,8, in diabetic group 62,0, and in IGT patients 63.4 years. Average fasting glycaemia in non-dibetic was 4,8 (0,8), in diabetics 8,3 (3.2) mmol/l and glycaemia during oG’IT (2 hours) was 7.2 (1,2) resp. 14.4 (3.3) mmol/l. P579 Accidentally found glycaemia during a day in newly detected diabetics Regeneration of Islet fiXells by Reg (Regenerating Gene): less than 8.0 mmol/l was found in 52,6%, glycaemia 8.1-15.0 in 39%, and ‘Ikanscriptional Activation of Reg Gene aud Identification of Reg over 15,O mmol/l in 8,4% of diabetic group. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Protein Receptor Conclusion: Despite the high prevalence of DM in the Czech Republic HIROSHI OKAMGTO, Takako Akiyama, Seiichi Kobayashi, Koji Nata, (5,7% of all inhabitants) and the long tradition of a very good organized Takayuki Ikeda, Naushcen J. Shervani, Kei Nakagawa, Shin Takasawa. care for diabetic patients in a special inpatient diabetic clinics, screening Biochemistry , Tohoku University Graduate School of M edicine, Sendni, programme in CR revealed in 2,43% of the investigated risk group of Miyagi, Japan inhabitants asymptomatically proceeding DM, and in 1.28% IGT. Track 4. Basic Research P578 Maltese Canadian Diabetes Survey M. MIHIC, V. Vuksan, P Corey, D.J.A. Jenkins, Z. Metelko, Z. Skrabalo, E. Vidgen. St.Joseph’s Health Centel; Toronto, Canada; Faculty of M edicine, University of Toronto, Canada; Institutefor Diabetes “Vuk Vrhovac’Zagreb, Croatia Maltese have an alarmingly high prevalence of Type 2 diabetes, 6.6% and IGT, 7.7% (WHO Malta Study, 1980). In 1990 a survey of stratified, randomly selected 655 Toronto residents of Maltese origin was conducted, with data gathered on biochemical, demographic, anthropometric, hereditary, nutritional and lifestyle parameters. The comparative analysis showed no difference between the native and expatriate populations in terms of prevalence rates or nutritional profile, thus putting in question the contribution due to dislocation factors such as emigration, changes in climate, culture and lifestyle. Significant relationships were seen between a) plasma insulin and various biochemical endpoints (triglycerides; r&30 p<O.OOl, HDL: r=-0.19 p<O.OOl, apolipoproteinsB; t=O.14 p<O.OOl and C3; r=O.12 pt0.005, uric acid; r=O.27 pt0.001, SBP; r&.25 pt0.001) and b) diagnostic status (NIDDM, IGT, normal) and antbropometry (waist/hip; mean=95 for NIDDM 92 for IGT, 0.89 for normal group, all mutually differentiated at pt0.05). Lifestyle factors such as level of physical activity and occupation played no significant role in NIDDM genesis. The follow-up phase of the Toronto study in 1996 involved 204 subjects randomly chosen from the original sample. The observed 6 year incidence was 10.6% IGT and 6.9% NIDDM. The major interest was in relationship of status change to the baseline characteristics (phase 1). Elevated serum lipids (TG; p-=0.002, TCYHDL; pt0.038). HbAlC: p-zO.001 and dietary fat for carbohydrate swap; pt0.031 are associated with progression to NIDDM. In addition to verifying the odds ratios for the Syndrome X risk cluster, several other candidates emerged to possibly augment the cluster, namely parental history of diabetes, C-peptide (fastingb660, postprandial>2564), apo-C3> 13.4 and apo-E> 14.1. Finally, the group of subjects who progressed from IGT to NIDDM was distinguished by a high ratio of postprandial to fasting insulin; 700:130 versus 500:160 for NlDDM and 350:90 for normal group. The Pancreatic islets have a limited capacity for regeneration, which predisposes them to tlte development of diabetes. In 1984, we found that the administration of poly(ADP-ribose) polymerase (PARP) inhibitors, such as nicotinamide (NA), to 90% depancreatized rats induced islet regeneration (Diabetes 33,401). We isolated a gene, Reg (regenerating gene) from a regenerating islet-derived cDNA library (JBC 263, 2111, 1988) and demonstrated that Reg protein induced ~-cell regeneration to ameliorate experimental diabetes (W AS 91, 3589, 1994; Endocrinology 139, 2369, 1998). Why Reg gene is expressed in regenerative processes of ~-cells and how Reg protein acts on p-cells to induce the proliferation have long been elusive. Here, we show the transcriptional activation of Reg gene by IL-6, dexamethasone (Dx) and NA, and the identification of a cell surface Reg protein receptor for islet regeneration. RT-PCR and immunoblot analyses revealed that the combined addition of IL-6 and Dx to RINmSF p-cells induced the Reg gene expression, and the induction was significantly enhanced by the addition of NA. The transcriptional activation of Reg gene was mediated by the -81--70 region (TGCCCCICCCAT) of rat Reg gene. Gel shift and Southwestern analyses revealed that the formation of the transcriptional active DNA/protein complex by IL-6/Dx was enhanced in the presence of NA. Therefore, IL-6 and glucocorticoids produced in regenerative processes such as insulitis activate Reg gene via the formation of the DNA/protein complex, and the induction of @cell regeneration by the administration of PARP inhibitors is achieved by the enhancement of the Reg gene activation. When the Reg gene is activated, the expressed Reg protein is secreted horn /l-cells and acts on p-cells as an autocrine/paracrine growth factor. We isolated a cDNA for the Reg protein receptor from a rat islet cDNA library by expression cloning. The cDNA encoded a cell surface 919 amino acid protein. The cells into which the cDNA had been introduced bound [‘2511Reg protein with high affinity (Kd = 4.4 nM). RNase protection assay revealed that the receptor mRNA was expressed in regenerating islets. We introduced the cDNA into RINm5F p-cells and established cell lines overexpressing the Reg receptor. The cell lines showed a significant increase in BrdU incorporation, and the cell number was greatly increased in response to Reg protein (0.3-100 nM), indicating that the cDNA encodes a Reg receptor for transducing the growth promoting signal of Reg protein to p-cells (JBC 275, 10723,ZOOO).