1. PANCREATIC HORMONES

2. Learning Objectives Physiological anatomy of pancreas Insulin
Chemical nature
Synthesis
Mechanism of action
Regulation of secretion
Physiological effects

3. ACINI secrete digestive juices
Islets of Langerhans
more in tail than body and head
Alpha cells % Glucagon
2. Beta cells %
Insulin, Amylin
3. Delta cells %
somatostatin
4. PP cells
Pancreatic Polypeptide

4. INSULIN
Protein made up of two amino acid chains which are connected to each other by disulfide linkages
Plasma half life of about 6 minutes
Free insulin in plasma is destroyed by INSULINASE in liver, kidneys and muscles

5. FORMATION OF INSULIN BETA CELLS 1. Endoplasmic reticulum
Insulin Preprohormone cleaved to Proinsulin
2. Golgi Apparatus
Proinsulin to insulin and peptide fragments

6. MECHANISM OF ACTION

7. With in seconds
Increase uptake of glucose by the translocation of GLUT-4 in muscles and adipose tissues
Permeable to K+, amino acids and phosphate

8. With in minutes
Change the activity levels of many intracellular enzymes
Hours to several days
Translation
Transcription

9. Learning Objectives Physiological effects of insulin
Glucagon (synthesis, chemical nature, regulation, physiological effects)
Somatostatin (regulation & physiological effects)

10. Physiological effects of Insulin
On Carbohydrate metabolism
Entry of glucose in cells of body (liver, muscle, adipose tissues)
Utilization of glucose as energy source except brain
Inhibition of gluconeogenesis
Storage of glycogen
Storage of fats

11. CARBOHYDRATE METABOLISM
INSULIN AND MUSCLES
During resting state
Slightly permeable to glucose and use free fatty acid for energy
During heavy or moderate exercise
Increase uptake of glucose in presence of low level of insulin because membrane becomes permeable (contraction)
After meals
High level of insulin causes increase uptake & use of glucose for energy and if muscles are not exercising excessive glucose is converted into glycogen.

12. INSULIN AND LIVER After Meal Increase uptake of glucose
Inactivation of glycogen phosphorylase (glycogen breakdown)
Increased activity of glucokinase (phosphorylation of glucose)
Increased activity of glycogen synthase
Excess glucose to fatty acid---triglyceride—LDL---adipose tissue
Between Meals
Decrease blood glucose decreases insulin, all steps in reverse

13. INSULIN AND BRAIN
Brain cells need glucose for energy and are permeable to glucose even in the absence of insulin
Hypoglycemic shock
When blood glucose level falls to 20 to 50 mg/100ml

14. Fat Metabolism Insulin acts as fat sparer
Synthesis of fats in liver (TG)
Transport through VLDL
Storage of TG in adipose tissues
Anabolic effect of insulin on fat metabolism

15. FAT METABOLISM INSULIN AND LIVER
Excessive glucose is converted into fatty acid
Fatty acid into triglycerides and then to LDL
Insulin activates lipoprotein lipase (capillary wall of adipose tissue) which converts triglycerides to fatty acids essential for absorption in adipose tissue cells

16. ADIPOSE TISSUES After the Meal
Insulin inhibits hormone sensitive Lipase
Increase glucose transport in adipose tissue and converted into glycerol phosphate which combines with fatty acids to form triglycerides
Between the Meals
Activation of hormone sensitive lipase
Lack of insulin in liver
Formation of phospholipids and cholesterol (atherosclerosis)
Increase beta oxidation resulting formation of Ketone bodies and KETOSIS

17. PROTEIN METABOLISM ANABOLIC Uptake of amino acids Transcription
Translation
Inhibits gluconeogenesis in liver
Inhibits catabolism

19. MECHANISM OF INSULIN SECRETION

21. Switching between carbohydrate & fat metabolism
Insulin
Glucagon
Growth hormone & cortisol
Epinephrine

22. GLUCAGON Secreted by alpha cells of the islets of Langerhans
Hyperglycemic hormone
Glucagon is protein in nature
Released in stressful & hypoglycemic conditions

23. Mechanism of action Through cAMP 2nd messenger system
Activation of glycogen phosphorylase
Synthesis of glucose-1phosphate
Release of glucose

24. EFFECT ON GLUCOSE METABOLISM
LIVER
G-protein coupled receptors
Glycogenolysis
Gluconeogenesis

25. OTHER EFFECTS
Activates adipose cell lipase
Inhibits storage of triglycerides in liver
Increases strength of heart
Enhances bile secretion
Inhibits gastric acid secretion

26. REGULATION OF SECRETION

27. SOMATOSTATIN Paracrine hormone Secreted by delta cells
Depresses the secretion of insulin and glucagon
Decrease the motility of stomach, duodenum and gall bladder
Decreases Secretion and absorption in GIT

28. REGULATION INCREASE SECRETION Increase blood glucose
Increase amino acid
Increase fatty acid
Gastrointestinal hormones released in response to food intake

29. SUMMARY OF BLOOD GLUCOSE REGULATION (24 hrs.)
Fasting blood glucose is 80 to 90mg/100 ml
Random blood glucose level is 120 to 140mg/100 ml
So the normal blood glucose is maintained by
Liver
Insulin and glucagon
Sympathetic nervous system (hypoglycemia)
Growth hormone and Cortisol (prolonged hypoglycemia)

30. DIABETES MELLITUS Definition:
A syndrome of chronic hyper glycaemia due to altered metabolism of carbohydrates, lipids & proteins caused by a decrease or total lack of insulin or diminished effectiveness of circulating insulin (insulin resistance).

31. Clinical features:
Greek word meaning large urine volume
Polyuria
Polydipsia
Polyphagia
Hyperglycemia
Glycosuria
Ketosis
Acidosis
coma

32. Classification OF DM
Type I diabetes, Insulin dependent diabetes mellitus (IDDM), Juvenile diabetes mellitus
Before age of 30
Type II diabetes, Non-Insulin dependent diabetes mellitus (NIDDM), Adult-onset diabetes
After age of 40
Secondary diabetes

33. CAUSES Type 1 Viral infections Autoimmune disorder Injury
Hereditary tendency

34. Type 2
Metabolic syndrome or syndrome X
Obesity
Insulin resistance
Fasting hyperglycemia
Lipid abnormalities
Hypertension

36. Secondary Diabetes Pancreatectomy Acute Pancreatitis
Chronic Pancreatitis
Haemochromatosis
Cushing's Disease
Acromegaly

37. CLINCAL PRESENTATION Blood glucose level 300 to 1200mg/100ml
Glycosuria
when blood glucose level rises to 180mg/100ml

38. Dehydration
Severe cell dehydration due to osmotic pressure in ECF
Osmotic diuresis
Polyuria
ECF dehydration
Polydipsia

39. Complications of Diabetes
VASULAR DAMAGE
High LDL, Atherosclerosis
A. Microvascular damage
Diabetic retinopathy
Diabetic nephropathy
B. Macrovascular damage
Stroke
Myocardial infarction
Diabetic neuropathy
Peripheral nerves
Autonomic nervous system

40. Ulceration and Gangrene of limbs
diabetic neuropathy + vascular damage
DIABETIC FOOT
Protein metabolism
Increased utilization and decreased storage
Weight loss despite of eating large (Polyphagia)
Asthenia (lack of energy)

41. Fat metabolism
Excessive Ketone Bodies formation
Leading to METABOLIC ACIDOSIS
Rapid and deep respiration ( KUSSMAUL BREATHING)
Kidneys try to compensate
When pH falls below 7 leads to ACIDOTIC COMA

43. DIAGNOSIS Urinary glucose Fasting blood glucose level
Normal 80 to 90mg/100ml
Blood insulin level
Type 1 low or undetectable
Type 2 high than normal
Acetone breath
Large amount of Acetoacetic acid is converted to Acetone which is volatile and vaporized in expired air

44. Glucose Tolerance Test

45. TREATMENT
Nutritional
Exercise
Monitoring
Pharmacologic
Education

46. Type 2 Sulfonylureas (increase insulin release)
Oral hypoglycemic agents
Sulfonylureas (increase insulin release)
Thiazolidinediones (reduce insulin resistance)
Biguanides or Metformin (reduced gluconeogensis)
INSULIN

47. Insulin therapy TYPE 1 Prepared by recombinant DNA method
Rapid acting—Humalog. peak min and last from 2-4 hours
Short acting—regular. peak in 2-3h and last for 4-6 hours.
Intermediate insulins—NPH. peak 4-12 hours and last hours.
Long acting—Humulin. peak h and lasts 20-30h.
Prepared by recombinant
DNA method

48. Combination insulins 70/30 (70% NPH and 30% regular)
Humolog 70/30 (Humolog and regular

49. HGB A1C Measures blood levels over 2-3 months
High levels of glucose will attach to hemoglobin

51. Insulinoma or Hyperinsulinism
Adenoma of islet of Langerhans
Increase insulin level
Severe hypoglycemia
Hypoglycemic Shock or Insulin shock
Immediate IV large quantities of glucose
IV Glucagon