Endocrine Physiology

For Regular Pharmacy Students-2015EC

BY ;
Adugnaw Ambelu (MSc)

University of Gondar

CMHS

Department of
Human Physiology
 Objectives
• At the end of this session the students will be able to:

 Mention chemical classes & solubility properties of

hormones

 Identify major endocrine glands & their hormones

 Describe major functions of each hormones

 Explain some disorders of each hormones

2
 Introduction
• Endocrinology
– Thomas Addison
• Endocrine system
– Gland and hormone
• Compare NS and ES in regulating
homeostasis
• What is gland?
• Types of glands?
• Candidate hormones?
3
 Introduction…
• Cell survival & function requires homeostasis

• Endocrine System is one of the major homeostasis regulating

systems of the body along with NS

• Regulates homeostasis via releasing of Hormones

4
 Functions of the Endocrine System
1. Homeostasis:

– Regulates ABP:AD,NAD, Ang-II, ANP, NO

– Thermoregulation: AD, NAD, T3/T4

– Mass change (bone, muscle, fat): GH, androgens

– Immuno-regulatory function: cortisol

– Regulates RBC formation: EPO, GH, T3 / T4, testosterone

– Ca2+ homeostasis: PTH, calcitonin

– Glucose homeostasis: insulin, glucagon

5
Functions of the Endocrine system…
2. Regulation of Reproduction:

– Gametogenesis

– Sexual desire

– Fertilization

– Fetal growth & development

– Nourishment of the newborn

3. Regulation of Body Growth & Development.

4. Production, utilization and storage of Energy.

6
 Components of the Endocrine system

• Glands/sending cell/sender

• Signal/Hormones

• Transport media: blood

• Receptors: specific

• Transducer proteins and 2nd messengers

• Amplifier: effector enzymes

• Response = Cellular Response

7
 Glands
• Cells or organs those synthesize & secrete chemical substances
for body to use or eliminate

• Glands are of two types

– Exocrine: secretion send via ducts

• Ducts carry secretion to surface or organ cavity

• Extracellular effects (e.g., Food digestion)

• Sweat, salivary, mucus and mammary gland

– Endocrine: secretion poured directly into bloodstream

8
Types of Glands

9
 Hormones
• “Hormone” from Gk hormaein=“excite”

• Hormones:

– Highly potent & specialized

– Produced by endocrine cells in response to specific stimuli

– Travel via bloodstream to target cells

– Bind with specific receptors of target cells

– Binding of hormone with receptors

• Initiate biological responses by target cells

10
 Hormones…
• Target cell responds to hormone

– B/c it bears receptors for the hormone

• Most hormones circulate in blood, coming into contact with

essentially all cells

• Each hormone has effect on ≥ one target tissues/cells

11
 Features of classical hormone

1. Must be produced by endocrine gland or cells

2. Released into blood or lymphatics without duct

3. Low blood concentration

– 10-12 to 10-9 mol/L

4. Needs a stimulus for its secretion

5. Acts on target cells, situated at distance

12
How hormones work?

13
Hormones…

14
 Chemical classes of hormones
1. Amines: tyrosine derivatives

– Catecholamines & thyroid hormones

2. Peptide/Protein: AA chain derivatives

– Most abundant type

– ADH, GH,TSH, FSH and LH

3. Steroids: cholesterol derivatives

– Adrenocorticoids, Sex hormones, Vit-D3

4. Eicosanoids: fatty acid derivatives

– Prostaglandins, Leukotrienes & Thromboxanes 15

Chemical classes of hormones…

16
 Hormone category based on Solubility
• Two classes based on solubility

1. Water soluble (Hydrophilic) hormones

✓ Catecholamines + Peptide/protein H.

✓ Receptors in/on surface of target tissue

2. Lipid soluble (Lipophilic) hormones

✓ Thyroid + Steroid H.

✓ Receptors inside cytoplasm or nucleus 17

Hormone synthesis, storage, release & transport

• Site of synthesis:

– Protein/peptide hormones: in the RER

– Steroid hormones: in the SER

• Storage:

– Protein/peptide hormones: preprohormones in vesicles

– Steroid hormones: cholesterol

• Release:

– Exocytosis
18
 Synthesis of peptide hormones

3/30/2023 19
Hormone Synthesis, Storage, Release &
Transport
• Transport:

– Hormones are transported in blood in two forms:

✓Free form by the blood: Peptide hormones & Catecholamine

✓Combined with plasma proteins (albumin & globulin)

✓Cortical steroid & Gonadal hormones

• Metabolism:

– metabolized in the liver or by target cells.

• Excretion:

– Urine, Feces, Sweat. 21

Hormone Receptors and Mechanisms of Action

• Hormones reach into the target tissue by diffusion.

– Binding of specific receptors at the target cell.

• Based on hormones solubility, receptors are found:

1. On the cell membrane

➢ Peptide hormones

➢ Catecholamine

2. Inside the cell

➢ Cytoplasm = Steroid hormones

➢ Nucleus = Thyroid hormones 22

 Hormone Receptors and MOA

Free Hormone 23
Bound with plasma protein
 How hormones bring a change?
• Hormones lead to biological changes via:

– Altering plasma membrane Permeability

– Regulating enzyme activity

– Induction of secretory activities

– Alter transport processes

– Growth: increasing rate of mitosis , apoptosis or via cell

differentiation
24
How hormones bring a change…

25
 MOA of hormones
Three Mechanisms

1.Direct membrane effect: H-R binding alter membrane

permeability by:

• Opening or closing of pores

• Conformational change of carriers

• Activation/inactivation of pump

2.Activation of second messengers

3.Direct activation of gene

26
MOA of Hydrophilic Hormones

27
MOA of lipophilic hormones

28
 Second messengers
• Common second messengers

1. Cyclic nucleotide

– cAMP (cyclic adenosine monophosphate)

• more important & widely spread

– cGMP (Cyclic guanosine monophosphate)

• Sildenafil helps to maintain cGMP

2. Phospholipids

– Inositol triphosphate (IP3) & Diacyl glycerol (DAG)

3. Ions like calcium 29

Second messenger system…

30
 Regulation of hormonal secretion
• Hormonal secretion is regulated by at least 3 mechanisms

1. Feedback regulatory mechanisms

– Negative feedback M. (most hormones)

– Positive feedback M. (LH- surge)

2. Nervous control

– Secretion of OT, ADH, AD, NA

3. Circadian rhythm (periodic variations)

– Cortisol, sex hormones, GH

31
32
 Physiological Functions Exhibit Circadian Rhythms

• All organisms (even plants) have alternating daily patterns of

rest & activity.
• Follow a 24-hour light-dark cycle & are known as circadian
rhythms
• Organisms when placed in conditions of constant light or
darkness, these activity rhythms persist, apparently cued by
an internal clock.
• In mammals, the 10 “clock” resides in suprachiasmatic
nucleus (SCN) of the hypothalamus
• 20 clocks influencing the behavior of different tissues.

33
Regulation of hormonal secretion…

34
Major endocrine glands

36
37
39
 Hypothalamus(HT)
• Part of the diencephalon, which forms the floor & the lateral
wall of the 3rd ventricle.

• Below thalamus

• < 1% of brain mass

• Plays most important role in controlling homeostasis

• The main brain structure involved in regulating hormonal

levels in the body

40
Hypothalamus(HT)…

41
 Hypothalamus(HT)…

Fig.Hypothalamo–Pituitary–Target Organ Relationships 42

 Function of Hypothalamus
• Endocrine function

–Controls pituitary gland secretion

• Synthesizes hypophysiotropic hormones

• Can be inhibiting or releasing hormone

• Stimulates synthesis of:

– Adenohypophyseal hormones

• Synthesizes Neurohypophyseal hormones

– ADH (vasopressin) & Oxytocin (OT)

43
Hypothalamic hormones (Neurosecretions)

44
Hypothalamus and Pituitary
glandMagnocellular
neurons

Pervicellular
neurons

45
Hypothalamic Hormones

46
Hypothalamic hormones

47
 Pituitary gland (hypophysis)

• Below hypothalamus

• Consists of 2 distinct parts

1. Anterior pituitary

– Adenohypophysis

– True gland

2. Posterior pituitary

– Neurohypophysis

– Not true gland

48
 Neurohypophysis

• Stores & releases ADH & Oxytocin

• Neuroendocrine cells from HT synapse directly on to blood

vessels in neurohypophysis

• As action potential arrives down axon,

– It releases hormones directly into bloodstream

• ADH & OT release is controlled by HT via neuroendocrine

reflexes
49
50
 Neurohypophysis: ADH
• Synthesized primarily by SON of HT

• Stored in posterior pituitary gland

• Released as osmo-receptor center is stimulated

• Function of ADH:

– Enhances H2O retention by kidney nephrons during urine

formation

– Contraction of arteriolar smooth muscle at high dose

51
 Neurohypophysis: ADH
• Factors stimulating release of ADH

– Hypovolemia (Hyperosmolality)

– Increased in Angiotensin-II
• Factors inhibiting the ADH release
– Hypervolemia: Pressure and volume receptors
– Drugs: alcohol, diuretics, AD, NA
– ANP

52
 Disorders of ADH secretion
• Hypo secretion of ADH: Diabetes insipidus

• Manifestation: Polyurea and polydipsia

Types: A. Central/ Neurogenic/Cranial DI

B. Peripheral/ Nephrogenic DI

How it differs from diabetes mellitus?

53
 Neurohypophysis: Oxytocin
• Formed 10 in Paraventricular nuclei of HT

• Functions of oxytocin:

– Induces uterus contraction (childbirth)

– Promotes milk ejection from mammary glands

(breasts) during breast-feeding

• Induces myoepithelial contraction (lactation)

– Creates social bonding b/n mother and child

54
 Neurohypophysis: oxytocin

• Factors stimulating oxytocin secretion

– Mechanical stimulation of nipple

– Reflexes from birth canal during birth

– Estrogen increases target cell sensitivity to OT

• Factors inhibiting oxytocin secretion

– Fear, pain, adrenaline & alcohol

55
OT

56
 Adenohypophysis
• Produces & secretes its own hormones

• Linked to HT by superior hypophyseal artery

• Regulated by HT & feedback from target glands

• HT secretes regulatory hormones into hypothalamo-

hypophyseal portal system

– Regulate secretions of adenohypophysis

57
Anterior pituitary cells and hormones

58
 Adenohypophysis…
• Produces Six Peptide Trophic Hormones:

59
Adenohypophysis…

60
Hormones of anterior & posterior pituitary
glands

61
Figure 18–9
 Growth/Somatotropic Hormone
• GH does not function through target gland

– But exerts its effects directly on almost all body tissues

Physiological effects of GH

• Promotion of linear growth(Height)

• Promotion of protein deposition in tissues

• Promotion of fat utilization for energy

• Impairment of CHO utilization for energy

62
 Physiologic Effects of GH
1. Decreases Carbohydrate Utilization

– Decrease glucose uptake in tissues

– Increase gluconeogenesis & glycogenolysis

– Increased GH increases blood glucose level

– Hence ↑insulin secretion

GH is Hyperglycemic hormone

– As a result, pancreatic ß-cells will be over busy & finally

burnt out leading to DM

Pituitary/Central DM 63
 Physiologic Effects of GH…

2. GH Enhances Protein
synthesis (Anabolic)
– Decreases catabolism of
proteins
3. GH Enhances Fat
catabolism(Lipolysis)
– Hence, GH enhances
protein synthesis, uses up
fat stores & conserves
carbohydrates
4. Other Roles of GH
• ↑RBC formation, ↑MR
64
Physiologic Effects of GH…

65
 Regulation of GH secretion

GH, SS, Cortisol Hormones

Androgens
Pregnancy, Estrogens
Aging, IGF-1 _ GHRIH (SS) + Insulin
T3/T4, PRL
GHRH Catecholamines
Stress Serotonin
Ghrelin
Surgical trauma OC MB
Anaesthesia +
Haemorrhage + Fasting/starvation
Excitement _
+ Exercise
+
Somatotrops
Hypoglycaemia
↓FFA
Deep sleep
AAs (arginine)
GH L-Dopa 66
 GH Abnormalities
1. Adolescent hypersecretion
– Gigantism/ Giantism
2. Adult hypersecretion:
– Acromegaly
3. Adult Hyposecretion: little
effect
– Progeria: occurs if deficit
is severe
4. Adolescent Hyposecretion
– Pituitary Dwarfism

68
 Gigantism
2.51m

Acromegaly

Dwarfism
54.6cm 69
70
 GH Abnormalities …

Progeria

3/30/2023 71
 Prolactin /Luteotropic hormone (LTH)
• Synthesized in anterior pituitary gland

• In females:

– Promotes growth & development of breast

– Enhances milk production/synthesis

– Delays ovulation

– Suppresses fertility by inhibiting action of LH and FSH

• PRL in males:

– ↑semen production, ↑Libido

72
Prolactin…

73
Endocrine axis

74
 Thyroid Gland
• It is the largest endocrine gland

• Contains two major specialised cells

1. Thyroid follicular cells

– Secrete T3/T4

2. Parafollicular cells

– Secrete calcitonin

75
 Biosynthesis of thyroid hormones
1. Iodide pump: iodide trapping
– Active uptake of iodide by sodium iodide symport (NIS):
2Na+ & 1 iodide ion
– Stimulated by TSH
– Concentrates iodide to ~ 30 times its concentration in blood
and even ~250 times when more active
– Iodide trapping: process of concentrating iodide

76
 Biosynthesis of thyroid hormones…
– Iodide is transported out of thyroid cells across apical side
into follicle by pendrin
• Epithelial cells also secrete into follicle thyroglobulin
– that contains tyrosine amino acids to which the iodine will
bind

77
 Biosynthesis of thyroid hormones…
2. Iodide ion oxidation:
– 2I- Peroxidase I2 (oxidation)
3. Thyroglobulin synthesis from CHO & AAs
– Within follicular cells & then released to colloid
4. Organification
– Iodine binds to TG
– Forming DIT & MIT in TG
– Oxidized iodine even in molecular form will bind directly
but slowly with tyrosine
– Facilitated thyroid peroxidase 78
 Biosynthesis of thyroid hormones…
5. Oxidative coupling of iodinated tyrosine

– After few minutes, hrs & even days, more & more of
iodotyrosine residues
become coupled with one another :

– DIT + MIT peroxidase 3,5,3’-Triiodotyronin (T3)

– DIT + DIT peroxidase 3,5,3’,5’-Tetraiodotyronin (T4)

– After coupling is complete

• Each TG contains 1-3 T4

• One T3 is found in 20-30% of TG 79

 Biosynthesis of thyroid hormones…

• Thyroid gland can store huge amount of thyroid hormones in

the form of TG in the colloid nearly enough for 2-3 months
supply

6. Pinocytosis of TG containing T3 & T4 by follicles

– Some TG will bind to megalin at apical membrane &

– then by forming complex, it will be transported to basal

membrane by transcytosis

80
 Biosynthesis of thyroid hormones…
7. Proteolytic cleavage of TG by lysosomal enzymes
– T4 and T3 released into fenestrated capillaries
• T4/T3 ratio=20:1
– ~ 75% iodinated tyrosine in TG remains in thyroid cells as
MIT & DIT
• Deiodinated by deiodinase
• I- will be reutilized
• Twice iodide provision than iodide pump for thyroid
hormone synthesis
• No MIT or DIT escapes from the gland
81
 Transport of T3 and T4
• 0.04% T4 and 0.4%T3 exist in free state
• Others are in bound form:
– 70% of T4 and T3 are transported in bound from with
thyroxin binding globulin(TBG)
– 10-15% is transported with transthyretin (..CNS)
– 15-20% is with albumin
– 3% with lipoproteins
• Being bound
– Prevents acute changes in thyroid function
– Prevents loss of the hormone via urine 82
 Thyroid hormones
• Thyroid follicular cells secrete
– ~ 93% T4, 7 % T3 and insignificant RT3
– Long duration of action & slow onset
• Almost all T4 is converted to T3 in peripheral tissues
– Mainly in liver, kidney and skeletal muscles
– Due to deiodinase
• T3 is ~ 4 times as potent/rapid as T4
– But T4 is present in blood in higher quantities & persists for
a much longer time compared with T3
84
 Functions of thyroid hormones
1. Calorigenic action

– ↑O2 consumption (↑oxidative metabolism)

– ↑Metabolic rate; Thermogenic

2. Essential for normal growth & development

– Bone, muscle, teeth, nerve tissue, epidermis in children

– Causes wakefulness, alertness, if excess it leads to

nervousness

– Increases memory and learning

85
 Function of thyroid hormones…
3. Metabolic function

– Enhances glucose synthesis, utilization and absorption

– ↑Protein synthesis , ↑Lipolysis

4. Effect on heart: +ve inotropic & chronotropic action

– Hypersecretion results in tachycardia

86
Disorders of T3/T4

88
 Goiter
• Generalized enlargement of thyroid gland

• Associated with euthyroidism, hyper or

hypothyroidism

• Causes:

– Endemic goiter: caused by Iodine

deficiency

– Tumourus goiter: due to adenoma or

carcinoma

– Physiologic goiter: puberty, pregnancy 89

 Calcium Homeostasis
• Normal plasma Ca2+ = 9.4 mg/dl

• Importance of Ca2+ in the body

• Muscle contraction

• Blood clotting

• Bone and teeth formation

• As a cofactor of enzyme activation

• Synaptic transmission

• Hormones involved in calcium homeostasis

– PTH, GH, Calcitriol, Calcitonin etc. 90

 Parathroid Hormone

• It is hypercalcemic Hormone

• Target organs : bone, Renal tubules & GIT

Effect of PTH on Bone

• Stimulates osteoclasts (bone resorption)

• Stimulates formation of new osteoclasts

• Transiently depresses osteoblasts (bone formation)

– The net effect is ↑[Ca2+] in blood

Effect of PTH on GIT

• ↑Absorption of Ca2+ in the small intestine 91

 Parathroid Hormone...
Effect of PTH on renal tubules
• ↑Reabsorption of Ca2+ in distal tubules & collecting duct
• ↑Formation of 1, 25 (OH)2 D3 at proximal tubules
Role of 1, 25 (OH)2 D3
• ↑Release of Ca++ from bone
• ↑Absorption of Ca++ in intestine
• ↑ Reabsorption of Ca++ in the renal tubules
Regulation of PTH secretion:
• ↓↓ [Ca2+] = ↑PTH secretion
• ↑↑[Ca2+] = ↓PTH secretion 92
 7-Dehydrocholestrol

Sun light

3- Cholecalciferol (Vit-D3)
Liver enzyme 25-α Hydroxylase

25-Hydroxycholecalciferol
Kidneys proximal tubules 1α-Hydroxylase Stimulated by PTH

1, 25-(OH)2 D3(vitamin D3)

• ↑ Synthesis of Ca-binding proteins
• ↑Ca absorption in GIT
• ↑Ca reabsorption in renal tubules 93
Vit-D deficiency

Causes

• Inadequate intake of Vit-D in diet

• Inadequate exposure to sunlight

• Inadequate absorption in GIT due to celiac disease

• Renal failure, failure to form calcitriol

Manifestation

• Hypocalcaemia = ↑PTH = ↑Ca mobilization =bone deformity

• In children: ↓↓Vit-D = Rickets i.e., bowing of limbs, retarded

bone growth, soft bone 94
 Calcitonin- Hypocalcemic Hormone

• It is hypocalcemic hormone (↓Ca++ level of blood)

Target organs: Bone, renal tubules & GIT

Effect on bone

•↓Activities of osteoclasts

•↓Formation of new osteoclasts

•↑Activities of osteoblasts
Effect on renal tubules: ↓Reabsorption of calcium

Effect on GIT: ↓Absorption and transport of calcium

95
 Adrenal/Suprarenal glands

• Consists of two components

1. Adrenal cortex: Outer part: steroid hormones

2. Adrenal medulla: Inner part

• Adrenal medulla produces two hormones (catecholamines)

1. Adrenaline/epinephrine

2. Noradrenaline/norepinephrine

96
 Adrenal glands…
• Adrenal cortex is
divided to 3
functional zones

97
Physiologic Effects of Catecholamines
1. Increases heart activity

2. Bronchodilator

3. Inhibits GI motility

4. ↑Mental alertness

5. ↑blood glucose level

↑ Lipolysis, ↑Utilization of fat

↑ Protein catabolism

6. ↑Metabolic Rate (MR)

When and how secreted? 98

Hormones of Adrenal Cortex

99
 Physiologic Effects of Cortisol
• Produced in response to stress
1. Metabolic Effects
– ↑BGC , ↑ lipolysis , ↑Protein catabolism
2. Immunosuppressant effect
– Inhibits lymphocyte activation & proliferation
3. Enhances catecholamine synthesis & release
4. Anti allergic action
5. Growth inhibitory effect
6. ↑HCl secretion, contributes to PUD
7. Stimulates surfactant production in lungs 100
Physiologic effects of Cortisol

101
 Aldosterone

• It is mineralocorticoid from adrenal cortex

Function

• ↑Na+ reabsorption Renal tubule

• ↑K+ & H+ secretion

• ↑Aldosterone = ↑Na+ = ↑Osmolality = ↑ADH

102
 Adrenal Androgens
▪ Produced in small amount mainly at Zona Reticularis

▪ Adrenal androgens: Dehydroepiandrosterone (DHEA) &

androstendione

▪ Both are converted to testosterone in circulation

▪ Androgens can be converted to estrogens in adipose tissue by

the aromatase enzyme
Aromatase
Androgens Testosterone Estrogen

103
 Adrenal androgens…
▪ Progesterone is formed in adrenal cortex as intermediate but
not normally released to blood

▪ Adrenal androgen secretion is primarily controlled by ACTH

Function of adrenal androgen

▪ Initiate development of 2o Sexual characteristics;

– Enlargement of genital organs

– Growth of hairs in axillary & pubic areas

104
 Pineal Gland
• Also called the pineal body or epiphysis.

• It is a small endocrine gland in the brain.

• The main hormone produced & secreted by the pineal gland is

melatonin.

• Production is stimulated by the suprachiasmatic nucleus

(SCN) in hypothalamus (primary center for circadian
rhythms)

✓ Light/dark changes required to synchronize.

105
 Pineal gland…
• Secretion is highest at mid night & b/n the ages of 0-5 years.

✓ Regulates the sleep-wake cycle by causing drowsiness and

lowering the body temperature

✓ Regulates the release of reproductive hormones in females.

For example, the timing, length, and frequency of

menstrual cycles in women are influenced by melatonin

106
The Endocrine Pancreas

107
 Endocrine Pancreas…
• Both endocrine & exocrine gland

• Endocrine cells (Islets of Larngerhans); 2% pancreatic tissue

• 4-types of endocrine cells

1. α-cells: 25%

2. β-Cells: 65%

3. δ-Cells: 8%

4. F-Cells: 2%

109
 Glucose Homeostasis

• Physiological range

• Beta cell produces insulin and amylin

• In normal metabolism glucagon dominates

• In feed state insulin to glucagon ratio is high

• In fast state insulin to glucagon ratio is low

110
Glucose Homeostasis …

111
 Insulin
• Insulin derived from Latin word insula meaning Island

• Secreted from Beta Cells of pancreatic islets

• Contains 51 amino acid residues

113
 Functions of Insulin
• Promotes glycogen, fat & protein synthesis

1. Metabolic Action

– ↑Glucose Transport & Utilization in many cells

– ↑Glycogenesis, ↓Glycogenolysis, ↓Gluconeogenesis

– ↑Protein Synthesis, ↑AA transport, ↓protein catabolism

– ↑Lipogenesis, ↓Lipolysis

2. ↑K+ transport into cells

3. Promotes body growth

114
 Regulation of insulin secretion

Exercise
GIT hormones
+ • Glucagon, GLP
Hyperglycemia + • Gastrin
+
• Secretin
Proteins + Factors
affecting insulin - SST
Parasympathetic +
stimulation Secretion of Stress
β-cells
-
+
Sympathetic
stimulation + Oral Hypoglycemic Drugs

Hyperkalemia↑K+

115
Mechanism of insulin secretion

116
 Disorders of insulin secretion
A. Excessive insulin secretion (Insulinoma)

– Leads to Hypoglycemia

B. Insulin deficiency (insulinopenia)

– Leads to Diabetes mellitus = Honey urine)

– Results in chronic disturbances in CHO, protein & fat

metabolism

– Characterized by persistent hyperglycemia, protein

catabolism and ketoacidosis.

117
 Clinical features of DM
• In the absence of insulin, glucose uptake by cells decreased,
and BGC > 200 mg/dl

1. Secondary to hyperglycemia there will be:

– Glycosuria (excessive glucose in urine)

– Polyurea (excessive urine out put)

– Hyperphagia (cell hunger)

– Polydipsia ( sensation of thirst)

118
 Clinical features of DM…
2. ↑Protein catabolism (asthenia)

– Body wasting, Weight loss, weakness

– ↑Amino acids in blood → ↑Gluconeogenesis → ↑BGC that

aggravates hyperglycemic complications.

3. ↑Lipolysis

– ↑FFA in blood

– ↑Glycerol in blood = ↑Gluconeogenesis → ↑BGC

4. Hyperkalemia (↑K+) → Nephropathy

119
 Clinical features of DM…
• Other complications associated with prolonged hyperglycemia:

– Diabetic retinopathy

– Diabetic neuropathy

– Atherosclerosis: hypertension, diabetic foot, loss of sensation

120
 Glucagon
• Made of 29 amino acids

• Produced from pancreatic α-cells

• Secreted when blood glucose

level falls

• Hyperglycemic hormone

• Analogy: glucagon is a knife that

cuts up glycogen

121
 Function of glucagon
1. On CHO metabolism
– ↑Glycogenolysis, ↑Gluconeogenesis
– Net effect is ↑blood glucose level
2. On Lipid metabolism
– ↑Lipolysis,↑Ketogenesis
3. On Protein: ↑protein catabolism
– Calorigenic effect

122
 Function of glucagon…
On CVS
– ↑Frequency of heart beat (HR)
– ↑Cardiac force of contraction by activating myocardiac
adenyly cyclase
– ↑BF in some tissues, esp. kidneys
•Enhances bile secretion
•Inhibits gastric acid secretion
•Natriuresis
•Stimulates insulin and GH secretion
123
 Regulation of glucagon secretion

Exercise

+
+ +
+
Factors
- Affecting + Stress
Parasympathetic
stimulation
glucagon
-
secretion SST
+ GIP
+
+

Insulin

124
 Summary
Recall at least one hormone for each gland?

125
Thank You!!!!

126