ME04 - Endocrine Pancreas Flashcards
INCREASED IN FED STATE
INCREASED
Insulin
Glucose oxidation
Glycogen synthesis
Fat synthesis
Protein Synthesis
INCREASED IN FAST STATE
INCREASED
Glycogenolysis
Gluconeogenesis
Ketogenesis
Secretes pancreatic juice to duodenum
Acini of Pancreas
Secretes insulin and glucagon directly into the blood
Islets of Langerhans of Pancreas
Cells in the Pancreas and Hormone it secretes
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_
Chemistry of INSULIN
Small protein with MW 5,808
Composed of two amino acid chains linked with 2 disulfide
bridges
Synthesis of INSULIN
Starts as insulin preprophormone from RER of beta cells
resulting to proinsulin
Proinsulin are cleaved in golgi apparatus»_space; insulin and
peptide fragments (proinsulin has no intrinsic activity)
What indicates there is an exogenous production?
Insulin preprohormone»_space; Proinsulin»_space; Insulin + C-peptide (C-peptide indicates the exogenous production)
Enzyme linked receptor of Insulin
Insulin Receptor»_space; has tyrosine activity (Combination of four subunits held together by disulfide linkages)
What are Insulin receptor subunits
_ Alpha subunits that lie entirely outside the cell membrane
_ Beta subunits that penetrate through the membrane, protruding into the cell cytoplasm
Steps in activating Insulin Receptor
Insulin binds to alpha subunit
Beta-subunit becomes autophosphorylated
Activation of local tyrosine kinase
Activation (phosphorylation) of Insulin-receptor
substrates
What are the End-effects of insulin to the body:
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
Carbohydrate Metabolism of Insulin in Muscle
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
Carbohydrate Metabolism of Insulin in Liver at “Feeding State”
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)
What are the effects of GLUCOSE IN THE LIVER
_ 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
Carbohydrate Metabolism of Insulin in Liver at “In Between Meals”
__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. _ _
What are the effects of GLUCOSE IN THE BRAIN
_ Brain can absorb glucose even without insulin.
_ Usually uses glucose only for metabolism (can use fats in
starvation phase)
Blood glucose less than 20-50 mg/dL
Hypoglycemia _ characterized by progressive nervous irritability that leads to fainting, seizures, and even coma.
Effects of INSULIN on FAT Synthesis
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»_space; increase in glycolysis_increase in pyruvate»_space; increase in Acetyl CoA
Excess of citrate and isocitrate ions is formed by the citric acid cycle. What enzyme is activated?
Acetyl-CoA carboxylase, first step in fatty acid synthesis is activated
What enzyme does INSULIN activate to promote TG
Insulin activates lipoprotein lipase in the capillary walls
of the adipose tissue. Triglycerides produced by liver released into bloodstream»_space; absorbed by adipose cells through lipoprotein lipase»_space; converted to triglyceride and stored
Effects of INSULIN on FAT Storage
Insulin inhibits the action of hormone-sensitive lipase
Insulin promotes glucose transport through the cell membrane into the fat cells
How does the INSULIN Stimulate in Protein Metabolism
_ 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
How does the INSULIN Inhibit in Protein Metabolism
_ 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
Factors that controls Insulin Secretion
_ 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
GI hormones that controls insulin secretion
Gastrointestinal hormones_gastrin, secretin,
cholecystokinin, and gastric inhibitory peptide. These hormones are released in GI tract
Other hormones that stimulate insulin secretion
Glucagon, growth hormone, cortisol, and, to a lesser
extent, progesterone and estrogen
What happens if you DECREASE INSULIN SECRETION?
DEC Glucose Uptake»_space; (Hyperglycemia, Glycosuria, Osmotic Diuresis, Electrolyte Depletion)
INC Protein Catabolism»_space; (INC plasma, amino acids, nitrogen loss in urine)
INC Lipolysis»_space; (INC plasma FFA, ketogenesis, ketonuria, ketonemia)
EVERYTHING»_space; Dehydration, Acidosis»_space; Coma, Death
Secreted by the alpha cells of the islets of Langerhans
Glucagon
Chemistry of Glucagon
Glucagon Has a molecular weight of 3485 and is composed of a chain
of 29 amino acids
Effect of GLUCAGON on Gluconeogenesis
Glucagon increase the rate of amino acid uptake by the liver cells and then the conversion of many of the amino acids to glucose
Effect of GLUCAGON on Glycogenolysis
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.
Most thoroughly studied pathway on secondary messenger
Has potent amplifying mechanism _ potent mechanism in increasing glucose
Glucagon on Glycogenolysis
Other effects of Glucagon
_ 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
Secreted by the delta cells of the islets of Langerhans
Somatostatin
Chemistry of Somatostatin
A polypeptide containing only 14 amino acids that has an
extremely short half-life
What is the function of Somatostatin:
Also known as growth hormone inhibitory hormone which
is secreted in the hypothalamus and suppresses anterior pituitary gland growth hormone secretion.
Somatostatin’s Inhibition functions include:
_ 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
PRINCIPAL ROLE of Somatostatin:
To extend the period of time over which
the food nutrients are assimilated into the blood.
SUMMARY OF GLUCOSE REGULATION
_ 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
A syndrome of impaired carbohydrate, fat, and protein metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissues to insulin
Diabetes Mellitus
Types of Diabetes Mellitus
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.
Due to injury of the beta cell of the pancreas (from viral or autoimmune disorders)
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
Decrease in insulin sensitivity
TYPE 2 DIABETES MELLITUS
_ Increased plasma insulin concentration (hyperinsulinemia)
_ Decreased insulin levels in the blood
_ Decrease in insulin sensitivity impairs carbohydrate
utilization and storage»_space; raising blood glucose»_space;
stimulating a compensatory increase in insulin secretion
Factors that is associated with metabolic syndromes:
_ Obesity
_ Insulin resistance
_ Fasting hyperglycemia
_ Lipid abnormalities such as increased blood
triglycerides and decreased blood high-density
lipoprotein-cholesterol
_ Hypertension
Major consequence of the metabolic syndrome and/or diabetes
Cardiovascular disease (atherosclerosis)
Difference of Absorption of Meal and Fasting
(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
Hormonal Regulation in the Absorptive State
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
Hormonal Regulation in the Post-Absorptive State
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)
