glucagon - regulation of blood glucose
TRANSCRIPT
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DR NILESH KATE
MBBS,MD
ASSOCIATE PROF
DEPT. OF PHYSIOLOGY
GLUCAGON
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OBJECTIVES. Source Chemistry Synthesis. Mechanism of action Actions of glucagon. Applied aspects. Blood glucose control
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WHERE IS THE PANCREAS?
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INTRODUCTION They constitute endocrine
part of pancreas. 1-2 million islets , more in
tail
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ISLETS OF LANGERHANS Four types of cells are
present in islets. They are A or alpha cells – secrete
Glucogon B or beta cells – secrete
Insulin D or delta cells – secrete
Somatostatin F or PP cells -- secrete
Pancreatic Polypeptide
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ENDOCRINE PANCREAS
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ISLETS OF LANGERHANS
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Pancreatic Hormones, Insulin & Glucagon Regulate Metabolism
Beta cells produce insulin – cellular uptake of blood glucose
Alpha cells produce glucagon – blood glucose (from cells)
D cells produce somatostatin – gastric secretion
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HISTOLOGICAL ORGANIZATION B CELLS, AT THE CORE A/D CELLS, AT THE PERIPHERY
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GLUCAGON Source of secretion :
A cells or Alpha cells of pancreas.
Chemistry : Glucagon is a polypeptide with a molecular weight of 3500.
It has 29 amino acid.
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SYNTHESIS From Preproglucagon
precursor by islets α cells.
Proglucagon
GLUCAGON.
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SECRETION. Stored in dense
granules Released by
Exocytosis. Ca is needed for
exocytosis.
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PLASMA LEVELS Circulating Glucagon – Unbound. Basal level in Fasting – 100-150 pg/ml. Half life – 6 min(5-9 min) Secretion Rate 100 -150 μg/day. Degradation – in liver & kidney
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MECHANISM OF ACTION
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ACTIONS OF GLUCAGON Mobilization of
stored nutrients Glucose, fatty acids,
ketoacids. Action exactly
opposite to insulin. Hormone of energy
release.
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ACTIONS OF GLUCAGON Effect of glucagon on carbohydrate
metabolism. Effect of glucagon on protein metabolism Effect of glucagon on fat metabolism. Other actions of glucagon .
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EFFECT OF GLUCAGON ON CARBOHYDRATE METABOLISM.
Increases Glycogenolysis in liver and not in muscle.
Glycogen Glucose-1-Phosphate
(inhibit Glycogen Synthetase)
Glucose
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EFFECT OF GLUCAGON ON CARBOHYDRATE METABOLISM.
Increases gluconeogenesis in liver.
Formation of Glucose from Lactate, Pyruvate, Glycerol & amino acids.
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EFFECT OF GLUCAGON ON FAT METABOLISM.
Increases lipolysis – excess FFA oxidized – energy production -ketogenesis in liver.
Increases release of FFA & Glycerol from adipose tissue and makes it available for peripheral utilization.
Prevents synthesis of triglycerides. Thus Glucagon – Ketogenic & Hyperglycemic
Hormone.
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EFFECT OF GLUCAGON ON PROTEIN METABOLISM
Increases Gluconeogenesis by increasing transport of Amino Acids into the liver.
Lowers plasma amino acids.
CALORIGENIC EFFECT Due to increased hepatic deamination of amino
acids
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OTHER ACTIONS OF GLUCAGON:
Inhibit renal tubular Na reabsorption – Natriuresis.
Increases Cardiac force of contraction – activation of myocardial Adenyl cyclase.
Stimulate secretion of growth hormone, insulin & Somatostatin
Regulation of appetite. Increases secretion of bile. Inhibits secretion of gastric juice.
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PLASMA GLUCOSE
Pancreatic islet alpha cells
GLUCAGONSECRETION
PLASMA GLUCAGON
Liver GLYCOGENOLYSIS GLUCONEOGENESIS KETONE SYNTHESIS
PLASMA GLUCOSE PLASMA KETONES
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REGULATION OF GLUCAGON SECRETION
Role of blood levels of Nutrients. Blood Glucose level – BSL
>70mg% stimulate Plasma amino acids-
protein rich meal specially Arginine & Alanine.
Free fatty acids & keto-acids – Negative feedback relationship.
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REGULATION OF GLUCAGON SECRETION
Role of GIT hormones – CCK-PZ, Gastrin, GIP stimulates
Role of Nervous system – sympathetic nerve stimulation – increases Stress, fasting, exercise,
infection – increases Vagal stimulation,
acetylcholine – increases.
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STIMULATORS OF GLUCAGON SECRETION
LOW PLASMA [GLUCOSE] AMINO ACIDS (ala, ser, cys, thr) GI HORMONES (CCK, gastrin) CORTISOL, GROWTH HORMONE EXERCISE INFECTIONS, other stresses -ADRENERGIC STIM, Ach
INSULIN/GLUCAGON
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INHIBITORS OF GLUCAGON SECRETION
ELEVATED PLASMA [GLUCOSE] SOMATOSTATIN SECRETIN FFA, KETONES INSULIN -ADRNERGIC STIM, GABA
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PANCREATIC HORMONES, INSULIN & GLUCAGON REGULATE METABOLISM
Metabolism is controlled by insulin and glucagon
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INSULIN VS. GLUCAGON
INSULIN Anabolic (building) hormone Increases glucose transport to
muscles and adipose for use Stores excess glucose in liver
and muscles as glycogen Lowers blood glucose Inhibits gluconeogenesis
(endogenous glucose production)
Promotes growth overall
GLUCAGON Catabolic (breaking down)
hormone Breaks down glycogen to
increase blood glucose level
Promotes gluconeogenesis
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REGULATION OF GLUCAGON
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REGULATION OF GLUCAGON
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HORMONAL REGULATION OF BLOOD GLUCOSE
Normal blood glucose levels & body glucose reserves.
Normal blood glucose levels. – Fasting blood glucose
levels -70-110 mg%. Postprandial – 140mg
%
GLUCOSE TOLERANCE CURVE.
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HORMONAL REGULATION OF BLOOD GLUCOSE
Normal body reserves of glucose. Free glucose –
currency of body 18 gms of free
glucose Enough for basal
energy requirement of body for 1 hour.
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STORED GLUCOSE. In the form of glycogen in liver & muscle Liver – 100 gms
Can provide 40-50 gms of glucose from glycogen
Can produce 125-150 mg of glucose Muscle –contains more glycogen than
liver But degradation does not produce glucose
directly but produce Lactate used for Gluconeogenesis.
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SOURCES OF BLOOD GLUCOSE. Dietary sources – Carbohydrates into
Monosaccharide's – into glucose Gluconeogenesis – from Lactate, Glycerol,
Propionate & amino acids Lactate – by degradation of muscle Glycogen. Free Glycerol & propionate by breakdown of fat in
adipose tissue. Amino acids from protein breakdown.
Glycogenolysis. From stored Glycogen in liver.
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UTILIZATION OF BLOOD GLUCOSE.
To provide energy need to body tissue Glycolysis & TCA cycle HMP shunt for pentoses & NADPH Uronic acid pathway
Glycogenesis. Synthesis of other Monosacchrides & amino
acids Synthesis of Fat.
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ROLE OF HORMONES IN REGULATION OF BLOOD GLUCOSE.
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PLASMA GLUCOSE
Adrenal medulla EPINEPHRINE SECRETION
PLASMA EPINEPHRINE
ACTIVITY OF SYMPATHETIC NERVESTO ADIPOSE TISSUE AND LIVER
Skeletal muscle GLYCOGENOLYSIS
Liver GLYCOGENOLYSIS GLUCONEOGENESIS
Adipose Tissue LIPOLYSIS
PLASMA GLUCOSE, FATTY ACIDS, GLYCEROL
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PREVENTION OF OCCURRENCE OF HYPERGLYCEMIA
Hyperglycemia after a carbohydrate meal or mixed meal is prevented by 4-5 times increase in INSULIN secretion. Increase uptake & utilization as chief fuel Promotes store of glucose as glycogen in liver & TG in
adipose tissue. Inhibit Gluconeogenesis & Glycogenolysis.
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PREVENTION OF OCCURRENCE OF HYPOGLYCEMIA.
There is only one hormone to prevent Hyperglycemia – Insulin
But 4 hormones to prevent Hypoglycemia Glycogen, Growth hormone,
Glucocorticoids & Epinephrine. Organs cannot use any fuel other
than glucose so vulnerable to Hypoglycemia are – Brain, Retina & Germinal Epithelium of gonads.
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PREVENTION OF OCCURRENCE OF HYPOGLYCEMIA.
Role of Glucagon – prevent Hypoglycemia between meals (few hours). Promotes Glycogenolysis & Gluconeogenesis. Lypolysis in adipose tissue& use FFA as chief fuel.
Role of Epinephrine (Many hours) – stimulate sympathetic nervous system through Hypothalamus Supplement actions of Glycogen Increase FFA production by lypolysis.
Role of growth hormones & Glucocorticoids(Few days) – decrease peripheral use of Glucose.
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Thank You
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