by yerukneh solomon(chenchaw) glucagon mechanism of action on protiens and carbo, gluccagon, insulin, insulin effect on protiens carbohydrates and fats, insulin synthesis and secretion, pancreatic polypeptide, somatostatin

1. Metabolic effects of
pancreatic hormones
By Yerukneh Solomon
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2. Outlines
 Introduction
 Pancreatic hormones synthesis and
secretion
 Pancreatic hormones effects on
metabolism
 Summary
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3. Introduction
Pancreas
 Pancreas contains exocrine & endocrine cells
 Roughly 99% of the cells of the pancreas are
arranged in clusters called acini.
The acini produce digestive enzymes, which flow into
the GIT.
 Endocrine cells are called Islets of Langerhans,
1-2% of pancreatic tissue.
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5. Introduc…
 There are 4-types of
endocrine cells
1. α-cells: secret
glucagon (25%)
2. β-Cells: secret
insulin (65%)
3. δ-Cells: secret
somatostatin (8%)
4. F-Cells: secret
pancreatic
polypeptides (2%)
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6. Insulin Chemistry and Synthesis
Insulin is a small protein;
human insulin has a molecular weight of 5808. It is
composed of two amino acid chains connected to each
other by disulfide linkages
Beta cells - beginning with translation of the insulin
RNA by ribosomes attached to the ER to form an insulin
preprohormone (11500) - cleaved in the ER to form a
proinsulin (9000) - further cleaved in the Golgi
apparatus to form insulin - secretory granules
unbound form; it has a plasma half-life that averages
only about 6 minutes - degraded by the enzyme
insulinase mainly in the liver, to a lesser extent in the7/18/2017 6

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11. Cellular effect of insulin
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12. Carbohydrate Metabolism
• Immediately after a high-carbohydrate meal, rapid
secretion of insulin occur
• The normal resting muscle membrane is only
slightly permeable to glucose, except when the
muscle
• fiber is stimulated by insulin
• Moderate or heavy exercise
• Few hours after a meal because of insulin –
Glucose stored as muscle GLYCOGEN – used
during anaerobic exercise
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14. Carbohydrate Metabolism
• Glucose absorbed after a meal to be stored
almost immediately in the liver in the form of
glycogen
 Insulin promotes storage by:
 Increasing the activity of the
Glucokinase,
 inactivating liver phosphorylase
 Increasing the activities of glycogen
synthase
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16. Carbohydrate Metabolism
Glucose Is Released from the Liver Between Meals
1. The decreasing blood glucose causes the
pancreas to decrease its insulin secretion.
2. Stopping further synthesis of glycogen in the
liver and preventing further uptake of glucose by
the liver from the blood.
3. The lack of insulin along with increase of
glucagon, activates the enzyme phosphorylase,
4. The enzyme glucose phosphatase, becomes
activated 7/18/2017 16

17. Carbohydrate Metabolism
• When the quantity of glucose entering the liver
cells is more than can be stored as glycogen,
Conversion of excess glucose into fatty acids
• Insulin also inhibits gluconeogenesis by:
 Decreasing the quantities and activities of the
liver enzymes required for gluconeogenesis
 Decreases the release of amino acids from
muscle and other extrahepatic tissues
• Brain cells use only glucose for energy
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18. Fat Metabolism
Insulin acts as fat sparer.
Promotes fatty acid synthesis in liver from excess
glucose
1. Insulin increases the transport of glucose into the
liver cells
2. Energy from glucose via citric acid cycle - excess
of citrate and isocitrate ions - activates acetyl CoA
carboxylase – acetyl CoA to form malonyl CoA
Fat storage in adipose tissue
 Fatty acids (triglycerides) are then transported from
the liver by way of the blood lipoproteins to the
adipose cells.
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19. Fat Metabolism
 Insulin promotes glucose transport into the fat
cells
 Insulin inhibits the action of hormone-sensitive
lipase
 insulin deficiency - free fatty acid
 FFA become main energy substrate
The excess of fatty acids in the plasma
promotes liver conversion of some of the fatty
acids into phospholipids and cholesterol
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21. Protein Metabolism and Growth
1. Insulin stimulates transport of many of the amino
acids into the cells
2. Insulin increases the rate of transcription of
selected DNA genetic sequences
3. Insulin increases the translation of mRNA
4. Insulin inhibits the catabolism of proteins
5. In the liver, insulin depresses the rate of
gluconeogenesis - conserves the amino acids in
the protein stores of the body
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23. fasting level of blood glucose of 80 to 90 mg/100 ml,
the rate of insulin secretion is minimal — 25 ng/min/kg
of body weight
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25. Glucagon and Its Functions
Glucagon, a hormone secreted by the alpha cells
of the islets of Langerhans when the blood
glucose concentration falls
Glucagon - large polypeptide - molecular weight
of 3485 – chain of 29 amino acids
1 µg/kg of glucagon can elevate the blood glucose
concentration about 20 mg/100 ml of blood (25 per
cent increase) in about 20 minutes
(1) breakdown of liver glycogen (glycogenolysis)
(2) increased gluconeogenesis in the liver
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26. Glucagon
 Synthesis, Secretion and metabolism
◦ Synthesized from the preprohormone
precursor called preproglucagon in the α-
cells of islets.
◦ Preproglucagon is converted into
proglucagon, which gives rise to
glucagon.
◦ Secreted from α-cells in the islets of
Langerhans of pancreas.
◦ It is also secreted from A cells of stomach
and L cells of intestine.
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27.  Chemistry And Half-life
◦ Polypeptide with a molecular weight of
3,485.
◦ It contains 29 amino acids.
◦ Half-life of glucagon is 3 to 6 minutes.
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28.  Metabolism
◦ About 30% of glucagon is degraded in liver
and 20% in kidney.
◦ The cleaved glucagon fragments are
excreted through urine.
◦ 50% of the circulating glucagon is
degraded in blood itself by enzymes such
as serine and cysteine proteases
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29.  Actions Of Glucagon
◦ Actions of glucagon are antagonistic
to those of insulin
◦ It increases:
 Blood glucose level,
 Peripheral utilization of lipids
 Conversion of proteins into glucose
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30. On Carbohydrate Metabolism
Glucagon increases the blood glucose level
by:
 Increasing glycogenolysis in liver.
 Increasing gluconeogenesis in liver
 Decreasing glycolysis
 Decreasing glycogenolysis
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31. Cellular effect of glucagon
 Glucagon causes glycogenolysis in
the liver, which in turn increases the
blood glucose concentration within
minutes.
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33. glycogenolysis
1. Glucagon activates adenylyl cyclase in the hepatic
cell membrane - cAMP - protein kinase,
2. Which activates phosphorylase b kinase,
3. Which converts phosphorylase b into phosphorylase
a,
4. Which promotes the degradation of glycogen into
glucose-1-phosphate,
5. Which then is dephosphorylated; and the glucose is
released from the liver cells.7/18/2017 33

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36. Gluconeogenesis
◦ by:
 Activating the enzymes, which convert
pyruvate into phosphoenol pyruvate
 Increasing the transport of amino acids into
the liver cells.
 The amino acids are utilized for glucose
formation
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38. Gluconeogenesis
increase the rate of amino acid uptake by the liver cells
and then the conversion of many of the amino acids to
glucose
activation of the enzyme system for converting pyruvate
to phosphoenolpyruvate, a rate-limiting step in
gluconeogenesis
glucagon activates adipose cell lipase, making
increased quantities of fatty acids available to the energy
systems of the body
Glucagon also inhibits the storage of triglycerides in
the liver, which prevents the liver from removing fatty
acids from the blood 7/18/2017 38

39. On Fat Metabolism
◦ Glucagon shows lipolytic and ketogenic actions.
◦ It increases lipolysis by increasing the release of
free fatty acids from adipose tissue and making
them available for peripheral utilization.
◦ The lipolytic activity of glucagon, in turn
promotes ketogenesis (formation of ketone
bodies) in liver
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40. ◦ In the adipocyte, glucagon activates
hormone- sensitive lipase,
 the enzyme that breaks down triglycerides
(stored fat) into diacylglycerol and free fatty
acids, releasing them into the circulation.
◦ Glycerol released into the circulation can
be utilized in the liver for gluconeogenesis
◦ Free fatty acids are used as fuel by most
tissues,
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43. Somatostatin
 Somatostatin is secreted from:
Hypothalamus
D cells (δ-cells) in islets of Langerhans of
pancreas
D cells in stomach and upper part of small
intestine.
 Somatostatin brings out its actions through cAMP
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44. Chemistry ,Half-life & metabolism
 Somatostatin is a polypeptide.
 It is synthesized in two forms, namely
somatostatin-14 and somatostatin-28
 Both the forms have similar actions.
 Half-life of somatostatin is 2 to 4 minutes.
 Somatostatin is degraded in liver and
kidney.
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45.  Actions Of Somatostatin
1. Somatostatin acts within pancreas,
inhibits β and α cells,
2. It decreases the motility of stomach,
duodenum and gallbladder
3. It reduces the secretion of gastrin, CCK,
GIP and VIP
4. Hypothalamic somatostatin inhibits the
secretion of GH and TSH
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46. Regulation Of Secretion Of Somatostatin
 Pancreatic Somatostatin
 Secretion of pancreatic somatostatin is
stimulated by glucose, amino acids and CCK.
 The tumor of D cells of islets of Langerhans
causes hypersecretion of somatostatin.
 It leads to hyperglycemia and other symptoms
of diabetes mellitus.
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47. Pancreatic Polypeptide
 Source Of Secretion
◦ Pancreatic polypeptide is secreted by F
cells or PP cells in the islets of
Langerhans of pancreas.
 Chemistry And Half-life
◦ Pancreatic polypeptide is a polypeptide
with 36 amino acids.
◦ Its half-life is 5 minutes.
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48. Synthesis and metabolism
 Pancreatic polypeptide is synthesized
from preprohormone precursor called
prepropancreatic polypeptide in the PP
cells of islets
 Pancreatic polypeptide is degraded and
removed from circulation mainly in
kidney.
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49. Actions Of Pancreatic
Polypeptide
◦ Exact physiological action of
pancreatic polypeptide is not known.
◦ It is believed to increase the secretion
of glucagon from α-cells in islets of
Langerhans.
 Pancreatic polypeptide brings out its
actions through cAMP.
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50.  Regulation Of Secretion
◦ Secretion of pancreatic polypeptide is
stimulated by the presence of chyme
containing more proteins in the small
intestine.
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51. Clinical correlations
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52. Hypoglycemia
 Hypoglycemia is common in insulin-treated
diabetic patients and also occurs occasionally in
patients treated with the oral hypoglycemic
sulfonylurea agents.
 Hypoglycemia may range from very mild lowering
of glycemia (60-70 mg/dl) with minimal or no
symptoms, to severe hypoglycemia with very low
levels of glucose (<40 mg/dl) and neurologic
impairment.
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54. Clinical correlation
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55. References
 Guyton & Hall:2011, Textbook of Medical
Physiology, 12th ed. Insulin, glucagon and DM
chapter XIV,
 Williams textbook of endocrinology, 13th
edition.
 Berney, and Levy, physiology, 6th edition.
 L. Sherwood, human physiology, 7th edition.
 Vander's, human physiology,11th edition.
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56. Thank You…
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