Pancreatic Regulation of Metabolism Flashcards
What is the role of glucokinase?
Converts glucose in the liver to G-6-P
What are the affects of insulin on the liver?
Increases glucokinase expression
Promotes glycogen synthesis
Promotes glycolysis
Inhibits glycogenolysis
Prevents release of glucose (represses expression of glucose-6-phosphatase)
Inhibits gluconeogenesis
Stimulates fatty acid synthesis
How does insulin inhibit gluconeogensis peripherally?
Inhibiting protein catabolism
When do liver glycogen levels peak?
4-6 hours after the ingestion of a meal
How can the enzyme profile of the liver change in response to the composition of one’s diet?
High Carb content - liver increase its production of enzymes that are essential for carb metabolism and fat synthesis
High protein content - increase in enzymes essential for AA metabolism and gluconeogenesis
How is glucose uptake by skeletal muscle regulated?
Primarily by insulin and to a lesser extent, increase in blood glucose
Stimulates translocation of the GLUT4 transporter
Can glycogen in skeletal muscle be mobilized to maintain blood glucose?
No, muscle lacks glucose 6-phosphatase
What is the effect of insulin on adipose tissue during the absorptive state?
Stimulate glucose uptake
What is the effect of insulin on lipoprotein lipase?
Induces its synthesis in skeletal muscle and fat cells
Catalyzes breakdgown of TAGs to fatty acids and glycerol
What is the effect of insulin on adipose tissue?
Inhibitor effect on basal and hormone-stimulated lipolysis by inhibiting hormone-sensitive lipase
What is the most potent physiological stimulator of hormone-sensitive lipase activity?
Epinephrine
What is the effect of insulin on ketogenesis?
Suppresses it by:
Indirectly inhibiting lipolysis in adipose tissue
Stimulating formation of malonyl CoA which blocks the transport of fatty acids into the mitochondria
What is the major control of hepatic ketone formation?
Flux of FA into the lvier
What is ketosis?
Accumulation of ketone bodies in tissue and body fluids
Can have toxic effects on tissue and cause acidosis
What is the effect of insulin on fatty acid synthesis?
Stimulates de novo FA synthesis in the liver
What is the effect of insulin on amino acid metabolism?
In skeletal muscle, insulin stimulates AA uptake and protein synthesis
Also inhibits proteolysis
What is the post-absorptive period?
3-5 hours after a meal, the body shifts from the use of exogenous fuel sources to endogenous reserves
What occurs to insulin and glucagon as the duration of a fast increases?
Insulin levels decline and glucagon levels rise
Causes a decrease in the insulin-glucagon ratio (most important in regulating metabolic functions in the liver
What are the two results of a decrease in circulating insulin during a fast?
Ensures glucose is shunted away from insulin-responsive tissue
Decreases the inhibitory influence of insulin on endogenous glucose production
What is the primary source of glucose during a fast?
Liver
What are the primary substrates for hepatic gluconeogenesis during a fast?
Amino acids and lactate from skeletal muscle
Lactate from RBCs
Glycerol from fat
What two tissue mobilize glucose for other tissues and why?
Liver and kidneys
Both express glucose-6-phosphatase
How does glucagon promote hepatic gluconeogenesis?
Increases activity of specific enzymes in the pathway
Insuring the flow of substrate to the gluconeogenic pathway by decreasing glycolytic enzymes
Promoting uptake of AAs by the liver
What substances are involved in the peripheral regulation of gluconeogenesis?
Cortisol - promotes protein catabolism
Insulin - inhibits protein catabolism
Describe the mobilization of fat reserves during fasting
Increase in the basal rate of lipolysis due to the removal inhibitory effect of insulin
Fatty acids are used as metabolic substrates, glycerol in used for gluconeogenesis
Increased deliver of fatty acids to the liver promotes ketogenesis
What occurs during the first three days of a fast?
Glucose mobilization from the liver due to insulin-glucagon ratio decrease
Increase in lipolysis
Increase in the breakdown of skeletal muscle protein
Growth hormone increases
What occurs about 3 days after fasting?
Plasma glucose, FFA, and glycerol levels stabilize
Ketones continue to increase
Sole source of glucose is gluconeogenesis
What occurs to the basal metabolic rate during prolonged fasting?
Basal metabolic rate goes down, most likely due to decreased thyroid hormone activity
T3 regulates the basal metabolic rate
During a fast, T3 drops by about half
What is the change in substrate utilization by the brain in a prolonged fast?
Goes from majority glucose to majority ketones
Transition to ketone metabolism has a protein sparing effect
What are the causes of hypoglycemia?
Drugs that potentiate the effects of insulin (SU) or substances that interfere with gluconeogenesis (EtOH)
Insulinomas
Rapid gastric emptying
Adrenal and Pituitary insufficiency
Liver disease
What is the response of the brain to hypoglycemia?
Hypothalamus activates the SNS
SNS stimulates glucagon release from pancreas
Rapid rise in circulating epinephrine levels
What causes the symptoms associated with hypoglycemia?
Sympathetic activation
Neuroglycopenia
What are counterregulatory hormones?
Hormones released in response to hypoglycemia
E.g. glucagon and epinephrine
What is the principal counterregulatory hormone in restoring blood glucose levels?
Glucagon
How does epinephrine protect against falling blood glucose?
Inhibiting glucose utilization by the muscle
Stimulating hepatic glycogenolysis and gluconeogenesis
Inhibiting insulin secretion and stimulating glucagon release
Stimulatory effect on lipolysis
What hormones are involved in the response to prolonged hypoglycemia?
GH and ACTH
What are the criteria for diagnosing DM?
Fasting plasma glucose >126 mg/dl
2h plasma glucose >200 during oral glucose tolerance test
AIC > 6.5
Symptoms of hyperglycemia
What is T1DM?
Insulin deficiency resulting from beta cell destruction
5-10%
What are the most serious acute metabolic complications of DM?
DKA and hyperosmolar hyperglycemic state
HHS is characterized by hyperglycemia, hyperosmolality and dehydration
What is T2DM?
Heterogeneous group of diseases characterized by a progressive impairment of beta cell function resulting in relative insulin deficiency plus varying degrees of insulin resistance
Obesity is a major risk factor
