ME04 - Endocrine Pancreas

Question 1

INCREASED IN FED STATE

Answer 1

INCREASED
Insulin
Glucose oxidation
Glycogen synthesis
Fat synthesis
Protein Synthesis

Question 2

INCREASED IN FAST STATE

Answer 2

INCREASED
Glycogenolysis
Gluconeogenesis
Ketogenesis

Question 3

Secretes pancreatic juice to duodenum

Answer 3

Acini of Pancreas

Question 4

Secretes insulin and glucagon directly into the blood

Answer 4

Islets of Langerhans of Pancreas

Question 5

Cells in the Pancreas and Hormone it secretes

Answer 5

Betacells - Secretes insulin and amylin
_60% of islet cells _
_Lies in the middle of each islet _

Alphacells - Secretes glucagon
_25% of islet cells _

Deltacells _- Secretes Somatostatin
Around 10% of total

PP cells - Secrets pancreatic polypeptide _ uncertain function
Minority in islet cells_

Question 6

Chemistry of INSULIN

Answer 6

Small protein with MW 5,808
Composed of two amino acid chains linked with 2 disulfide
bridges

Question 7

Synthesis of INSULIN

Answer 7

Starts as insulin preprophormone from RER of beta cells
resulting to proinsulin
Proinsulin are cleaved in golgi apparatus&raquo_space; insulin and
peptide fragments (proinsulin has no intrinsic activity)

Question 8

What indicates there is an exogenous production?

Answer 8

Insulin preprohormone&raquo_space; Proinsulin&raquo_space; Insulin + C-peptide (C-peptide indicates the exogenous production)

Question 9

Enzyme linked receptor of Insulin

Answer 9

Insulin Receptor&raquo_space; has tyrosine activity (Combination of four subunits held together by disulfide linkages)

Question 10

What are Insulin receptor subunits

Answer 10

_ Alpha subunits that lie entirely outside the cell membrane
_ Beta subunits that penetrate through the membrane, protruding into the cell cytoplasm

Question 11

Steps in activating Insulin Receptor

Answer 11

Insulin binds to alpha subunit
Beta-subunit becomes autophosphorylated
Activation of local tyrosine kinase
Activation (phosphorylation) of Insulin-receptor
substrates

Question 12

What are the End-effects of insulin to the body:

Answer 12

Increase in glucose uptake in majority of the cells in the body_ due to translocation of multiple intracellular vesicles to the cell membranes
Except brain, RBCs, intestinal mucosa, kidneys, beta cells of pancreas (BRICK-L)
Cell membrane becomes more permeable to many of the amino acids, potassium ions, and phosphate ion
Phosphorylation or dephosphorylation of metabolic enzymes
Upregulation of transcription and translation to promote cell growth

Question 13

Carbohydrate Metabolism of Insulin in Muscle

Answer 13

On Muscle
Normal resting muscle is only slightly permeable to glucose _ Energy source of muscles in between meals is from fatty acids
Post-prandial rise of insulin results to increase uptake of glucose by muscles
Abundance of glucose in muscles that are not used is stored in the form of glycogen

Question 14

Carbohydrate Metabolism of Insulin in Liver at “Feeding State”

Answer 14

Most of the glucose absorbed after a meal to be stored almost immediately in the liver in the form of glycogen
In between meals, glycogen is then mobilized to maintain blood glucose levels (WARNING! This is not directly controlled by insulin)

Question 15

What are the effects of GLUCOSE IN THE LIVER

Answer 15

_ Inactivates liver phosphorylase
_ Enhanced uptake of glucose from the blood by the liver
cells
_ Activates glycogen synthase _ enzyme used for polymerization of monosaccharide to glycogen

Question 16

Carbohydrate Metabolism of Insulin in Liver at “In Between Meals”

Answer 16

__Activates liver phosphorylase _ causes splitting of glycogen into glucose phosphate _

__Decreasing blood glucose causes the pancreas _ to decrease its insulin secretion

_ ___Lack of insulin then reverses all the effects__ listed earlier for glycogen storage, essentially stopping further synthesis of glycogen in the liver and preventing further uptake of glucose by the liver from the blood _ _

___Activates the enzyme phosphorylase, which causes the splitting of glycogen into glucose phosphate. _ _

Question 17

What are the effects of GLUCOSE IN THE BRAIN

Answer 17

_ Brain can absorb glucose even without insulin.
_ Usually uses glucose only for metabolism (can use fats in
starvation phase)

Question 18

Blood glucose less than 20-50 mg/dL

Answer 18

Hypoglycemia _ characterized by progressive nervous irritability that leads to fainting, seizures, and even coma.

Question 19

Effects of INSULIN on FAT Synthesis

Answer 19

Insulin promotes utilization of glucose, ERGO, spares fats as source of energy
Insulin promotes fat synthesis
It increases the transport of glucose into the liver cells&raquo_space; increase in glycolysis_increase in pyruvate&raquo_space; increase in Acetyl CoA

Question 20

Excess of citrate and isocitrate ions is formed by the citric acid cycle. What enzyme is activated?

Answer 20

Acetyl-CoA carboxylase, first step in fatty acid synthesis is activated

Question 21

What enzyme does INSULIN activate to promote TG

Answer 21

Insulin activates lipoprotein lipase in the capillary walls
of the adipose tissue. Triglycerides produced by liver released into bloodstream&raquo_space; absorbed by adipose cells through lipoprotein lipase&raquo_space; converted to triglyceride and stored

Question 22

Effects of INSULIN on FAT Storage

Answer 22

Insulin inhibits the action of hormone-sensitive lipase
Insulin promotes glucose transport through the cell membrane into the fat cells

Question 23

How does the INSULIN Stimulate in Protein Metabolism

Answer 23

_ Insulin stimulates transport of many of the amino acids into the cells
_ Insulin increases the translation of messenger RNA, thus forming new proteins
_ Insulin also increases the rate of transcription of selected DNA genetic sequences in the cell nuclei, thus forming increased quantities of RNA and still more protein synthesis

Question 24

How does the INSULIN Inhibit in Protein Metabolism

Answer 24

_ Insulin inhibits the catabolism of proteins, thus decreasing the rate of amino acid release from the cells
_ In the liver, insulin depresses the rate of gluconeogenesis

Question 25

Factors that controls Insulin Secretion

Answer 25

_ Increase in blood glucose results to increase in insulin secretion _ Increase in arginine and lysine stimulates insulin secretion _ Insulin in turn promotes transport of amino acids into the tissue cells as well as intracellular formation of protein

Question 26

GI hormones that controls insulin secretion

Answer 26

Gastrointestinal hormones_gastrin, secretin, cholecystokinin, and gastric inhibitory peptide. These hormones are released in GI tract

Question 27

Other hormones that stimulate insulin secretion

Answer 27

Glucagon, growth hormone, cortisol, and, to a lesser extent, progesterone and estrogen

Question 28

What happens if you DECREASE INSULIN SECRETION?

Answer 28

DEC Glucose Uptake >> (Hyperglycemia, Glycosuria, Osmotic Diuresis, Electrolyte Depletion) INC Protein Catabolism >> (INC plasma, amino acids, nitrogen loss in urine) INC Lipolysis >> (INC plasma FFA, ketogenesis, ketonuria, ketonemia) EVERYTHING >> Dehydration, Acidosis >> Coma, Death

Question 29

Secreted by the alpha cells of the islets of Langerhans

Answer 29

Glucagon

Question 30

Chemistry of Glucagon

Answer 30

Glucagon Has a molecular weight of 3485 and is composed of a chain of 29 amino acids

Question 31

Effect of GLUCAGON on Gluconeogenesis

Answer 31

Glucagon increase the rate of amino acid uptake by the liver cells and then the conversion of many of the amino acids to glucose

Question 32

Effect of GLUCAGON on Glycogenolysis

Answer 32

Glucagon promotes glycogenolysis in the liver _ Glucagon activates adenylyl cyclase in the hepatic cell membrane _ Which causes the formation of cyclic adenosine monophosphate, _ Which activates protein kinase regulator protein _ Which activates protein kinase _ Which activates phosphorylase b kinase _ Which converts phosphorylase b into phosphorylase a _ Which promotes the degradation of glycogen into glucose-1-phosphate, _ Which then is dephosphorylated; and the glucose is released from the liver cells. _ Activates the enzyme phosphorylase, which causes the splitting of glycogen into glucose phosphate.

Question 33

Most thoroughly studied pathway on secondary messenger Has potent amplifying mechanism _ potent mechanism in increasing glucose

Answer 33

Glucagon on Glycogenolysis

Question 34

Other effects of Glucagon

Answer 34

_ Glucagon activates adipose cell lipase, making increased quantities of fatty acids available to the energy systems of the body _ Enhances the strength of the heart _ Increases blood flow in some tissues, especially the kidneys _ Enhances bile secretion _ Inhibits gastric acid secretion

Question 35

Secreted by the delta cells of the islets of Langerhans

Answer 35

Somatostatin

Question 36

Chemistry of Somatostatin

Answer 36

A polypeptide containing only 14 amino acids that has an extremely short half-life

Question 37

What is the function of Somatostatin:

Answer 37

Also known as _growth hormone inhibitory hormone_ which is secreted in the hypothalamus and suppresses anterior pituitary gland growth hormone secretion.

Question 38

Somatostatin's Inhibition functions include:

Answer 38

_ Somatostatin acts locally within the islets of Langerhans themselves to depress the secretion of both insulin and glucagon _ Somatostatin decreases the motility of the stomach, duodenum, and gallbladder _ Somatostatin decreases both secretion and absorption in the gastrointestinal tract

Question 39

PRINCIPAL ROLE of Somatostatin:

Answer 39

To extend the period of time over which the food nutrients are assimilated into the blood.

Question 40

SUMMARY OF GLUCOSE REGULATION

Answer 40

_ The liver functions as an important blood glucose buffer system _ Both insulin and glucagon function as important feedback control systems for maintaining a normal blood glucose concentration _ In severe hypoglycemia, a direct effect of low blood glucose on the hypothalamus stimulates the sympathetic nervous system. _ Over a period of hours and days, both growth hormone and cortisol are secreted in response to prolonged hypoglycemia

Question 41

A syndrome of impaired carbohydrate, fat, and protein metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissues to insulin

Answer 41

Diabetes Mellitus

Question 42

Types of Diabetes Mellitus

Answer 42

Type 1 diabetes, insulin-dependent diabetes mellitus (IDDM), is caused by lack of insulin secretion. Type 2 diabetes, non_insulin-dependent diabetes mellitus (NIDDM), is caused by decreased sensitivity of target tissues to the metabolic effect of insulin. This reduced sensitivity to insulin is often called insulin resistance.

Question 43

Due to injury of the beta cell of the pancreas (from viral or autoimmune disorders)

Answer 43

TYPE 1 DIABETES MELLITUS _ Decreased insulin levels in the blood Sequelae of decreased insulin production _ Increased blood glucose _ Increased utilization of fats for energy _ Depletion of body protein

Question 44

Decrease in insulin sensitivity

Answer 44

TYPE 2 DIABETES MELLITUS _ Increased plasma insulin concentration (hyperinsulinemia) _ Decreased insulin levels in the blood _ Decrease in insulin sensitivity impairs carbohydrate utilization and storage >> raising blood glucose >> stimulating a compensatory increase in insulin secretion

Question 45

Factors that is associated with metabolic syndromes:

Answer 45

_ Obesity _ Insulin resistance _ Fasting hyperglycemia _ Lipid abnormalities such as increased blood triglycerides and decreased blood high-density lipoprotein-cholesterol _ Hypertension

Question 46

Major consequence of the metabolic syndrome and/or diabetes

Answer 46

Cardiovascular disease (atherosclerosis)

Question 47

Difference of Absorption of Meal and Fasting

Answer 47

(ABSORPTION OF MEAL INC GLUCOSE) INC Insulin | INC Insulin/Glucagon Ratio DEC Glucagon Formation of Glycogen, Fat and CHON DEC Blood, Glucose, AA, FA, Ketone Bodies (FASTING DEC GLUCOSE) DEC Insulin | INC Insulin/Glucagon Ratio INC Glucagon Hydrolysis of glycogen, fat and protein + Gluconeogenesis and Ketogenesis INC Blood, Glucose, AA, FA, Ketone Bodies

Question 48

Hormonal Regulation in the Absorptive State

Answer 48

ABSORPTIVE STATE: Absorption of energy 4H period after eating INC Insulin Secretion (INSULIN _ major hormone that promotes anabolism) INC Blood Insulin Cellular uptake of glucose Stimulate glycogen storage in liver & muscles Triglycerides storage in AA Promote cellular uptake of AA & Synthesis of proteins

Question 49

Hormonal Regulation in the Post-Absorptive State

Answer 49

POST-ABSORPTIVE STATE: Fasting State At least 4H after meal INC in glucagon secretion Maintains blood glucose concentration When blood (glucagon) increased. Stimulates glycogenolysis in the liver (G6 Phosphate) Stimulates gluconeogenesis Skeletal muscle, heart, liver & kidneys use fatty acids as major source of fuel Stimulates lipolysis & ketogenesis (Hormone-sensitive lipase)