1

2

PANCREATIC HORMONES

Dr.Mohammed Sharique Ahmed QuadriAssistant professorAlmaarefa College

3

Objectives• Describe the functional anatomy of the pancreas

• List all pancreatic hormones

• Describe the regulation of pancreatic hormone secretions

• Illustrate the mechanisms of action of insulin and glucagon

• Discuss the physiological effects of insulin and glucagon

4

Interconversions Among Organic Molecules

• Food intake is intermittent – nutrients must be stored for use between meals– Excess circulating glucose

• Stored in liver and muscle as glycogen• Once liver and muscle stores are “filled

up”, additional glucose is transformed into fatty acids and glycerol and stored in adipose tissue

– Excess circulating fatty acids• Become incorporated into triglycerides

– Excess circulating amino acids• Converted to glucose and fatty acids

5

Stored Metabolic Fuel in the Body

6

Comparison of Absorptive and Postabsorptive States

• Absorptive state– Fed state– Glucose is plentiful

and serves as major energy source

• Postabsorptive state– Fasting state– Endogenous energy

stores are mobilized to provide energy

7

Roles of Key Tissues in Metabolic States• Liver

– Primary role in maintaining normal blood glucose levels– Principal site for metabolic interconversions such as

gluconeogenesis• Adipose tissue

– Primary energy storage site– Important in regulating fatty acid levels in the blood

• Muscle – Primary site of amino acid storage– Major energy user

• Brain– Normally can only use glucose as an energy source – Does not store glycogen

• Mandatory blood glucose levels be maintained

8

Pacreas

Endocrine Pancreas

• 1-2 million islets are present.

• Each is richly supplied by blood that finally drains in to the Portal Vein.

9

The Endocrine Pancreas (Islets of Langerhans)• Beta (B cells)

– 60-70% of islet cells– Insulin

• Alpha (A cells)– 20 -25% of islet cells– Glucagon

• Delta (D cells)– 10% of islet cells– Somatostatin

• F (PP) cells– Approx 1% of islet cells– Pancreatic polypeptide

Insulin and glucagon areMost important in regulating fuel metabolism 10

11

Pancreatic Hormones• Insulin

– Anabolic hormone– Promotes cellular uptake of glucose, fatty acids,

and amino acids and enhances their conversion into glycogen, triglycerides, and proteins, respectively

• Lowers blood concentration of these small organic molecules

– Secretion is increased during absorptive state• Primary stimulus for secretion is increase in blood

glucose concentration

12

Glucose Levels and Insulin Release from the Beta Cells

Short half life (3-6 min)

The Insulin Receptor•Membrane glycoproteins composed of 2 subunits

• sub unit has Tyrosine kinase activity

•Sequence of events:Binding of insulin to

site unit trigger the autophosphorylation of tyrosine kinase of sub unit. Thus insulin exerts its biological action.

14

Factors affecting blood glucose

ACTIONS OF INSULIN1.CARBOHYDRATE METABOLISM

: Promotes glucose uptake & storage: Promote glycogenesis( synthesis of glycogen from glucose)

Increases activity of Glycogen Synthetase Inhibits Glycogenolysis( breakdown of glycogen into glucose)

Inactivates liver Phosphorylase thus in liver. Inhibits Gluconeogenesis by( Conversion of AA into glucose)

decreasing the activity of liver enzymes necessary for gluconeogenesis.

Increases activity of Glucokinase. This causes initial phosphorylation of glucose after it diffuses

into the cells.Therefore net effect is To increase glycogen synthesis in liver. To decrease glucose in blood

1.CARBOHYDRATE METABOLISM

– Muscle– It increases glucose entry by increasing

GLUT4.– Increases storage of glycogen

– Adipose tissue • Promotes glucose entry [GLUT4.] which is then

used to form glycerol phosphate.

• This provides the glycerol which combines with fatty acids to form triglycerides thus promoting deposition of fat.

17

Glucose Transporters Recruitment

• Insulin increases glucose uptake in most of the cells by GLUT4 ( glucose transporters)

• GLUT4 operates only after binding with insuline.

• In insuline dependent cells GLUT4 are retrieved from plasma membrane when insulin secretion decreases

18

Tissue that do not depend on insuline for glucose uptake

• BRAIN

• WORKING(EXERCISING MUSCLES)

• LIVER

Action of insulin on PROTEIN METABOLISM

insulin decreases blood amino acid level & stimulate protein synthesis. Promotes active transport of A.A in muscles and

other tissue s

Stimulates protein synthesis in cell

Inhibits protein breakdown

20

Action of insuline on FAT METABOLISM

• Decrease blood fatty acid level & promotes Triglyceride storage – Promotes entry of FA into adipose tissue cells – Promotes entry of glucose into adipose tissue

cells- precursors for FA & glycerol, raw material for synthesis of Triglycerides

– Promotes synthesis of TG from FA and glycerol– Inhibits lipolysis hence release of FA from adipose

tissue

• Other Effects of insuline 1. Helps in general growth along with other

hormones.

2. On electrolytes causes increased entry of K+ into cells thereby decreasing plasma K+ levels.

23

Factors controlling insuline secretion

24

Pancreatic Hormones

• Glucagon– Mobilizes energy-rich molecules from storage sites

during postabsorptive state– Secreted in response to a direct effect of a fall in

blood glucose on pancreatic α cells– Generally opposes actions of insulin

Glucagon is the hormone of "starvation." - It produces hyperglycemia

25

Blood Glucose and the Pancreatic Hormones

Actions of Glucagon ON CARBOHYDRATE: Stimulates hepatic glycogenolysis. Increases gluconeogenesis.ON FAT: Promotes fat breakdown and inhibits triglyceride syntheis - FFA and glycerol in blood -used for gluconeogenesis - Oxidation for energy (Ketogenesis) ON PROTEIN: Inhibits protein synthesis - Proteolytic Effects

• Glycogenolytic, Gluconeogenic, Lipolytic, Ketogenic Hormone.

27

COMPLEMENTARY INTERACTION OF GLUCOSE AND INSULINE

28

Counteracting action of insulin & gluccagon during absorption of high protein

SomatostatinReleased from pancreatic D cells in direct response to increase in blood sugar and blood amino acids during absorption of a meal

• Inhibitory effect on both insulin and glucagon• Decreases motility of stomach, duodenum and

gallbladder• Decreases secretion and absorption in the

gastrointestinal tract

• End result1. Inhibits digetion and absorption of nutrients2. Decreased utilization of absorbed nutrients by tissues3. Extends the availability of nutrients for longer periods of

time

References

• Human physiology by Lauralee Sherwood, seventh edition

• Text book physiology by Guyton &Hall,11th edition

• Text book of physiology by Linda .s contanzo,third edition