name normal blood glucose levels
- fasting: 70-110 mg/dL
- 2 hours postprandial: <120 mg/dL
- if <55 mg/dL
- results in hypoglycemia with adrenergic or neuroglycopenia
the half-life of insulin and glucose is ~___ min
4-6 min
post-prandial increase of glucose leads to increase of _____ and decrease of _____
post-prandial increase of glucose leads to increase of insulin and decrease of glucagon
the ____ level drops only 25% and is ready to be raised during fasting
why is _____ always present?
the glucagon level drops only 25% and is ready to be raised during fasting
hypoglycemia is much worse than hyperglycemia, always have basal levels of glucagon since you don’t want to waste time synthesizing it in times of need
describe the synthesis of insulin
preproinsulin -> proinsulin -> human insulin
- preproinsulin has disulfide side groups that need help connecting and creating disulfide bonds
- the leader sequence is cleaved and this creates proinsulin that has disulfide bonds
- C-peptide is cleaved in proinsulin to make human insulin
describe the function of the C-peptide
helps to form the disulfide bonds with precision
- the A-chain has 2 adjacent cysteine residues
- the first forms the intrachain disulfide bond in the A-chain
- the second forms the interchain disulfide bond with the B-chain
describe the function of the liver after a meal
- uptake of dietary sugars slows down the increase of blood glucose
- insulin stimulates hepatic:
- glycogen synthesis
- fatty acids synthesis
- cholesterol synthesis
describe the function of the liver during fasting
- release of free glucose into the blood prevents drop of blood glucose
- glucagon stimulates hepatic:
- glycogen degradation
- gluconeogenesis
- fatty acid degradation
glycogen is the storage form of glucose and is found in _____
glycogen is the storage form of glucose and is found in cytosolic glycogen granules
glycogen degradation is stimulated by _____ and _____
- glucagon and epinephrine
the _____ structure of glycogen allows rapid release of many free glucose molecules into the blood
the branched structure of glycogen allows rapid release of many free glucose molecules into the blood
what is needed for gluconeogenesis
- alanine, lactate and glycerol (provided by the blood)
during fasting, which 2 organs perform gluconeogenesis?
liver and kidney
low blood glucose levels activate which systems?
- pituitary gland release ACTH -> cortisol (gluconeogenesis)
- autonomic nervous system releases catecholamines (glycogenolysis) and glucagon (both glycogenolysis and gluconeogenesis)
- alpha-cells of the pancreas release glucagon
describe adrenergic symptoms
- occurs abruptly when the blood glucose levels fall
- epinephrine is released and is stimulated by the regulation of the hypothalamus
- symptoms:
- anxiety
- palpitation
- tremors
- sweating
describe neuroglycopenia symptoms
- occurs from a gradual decline
- the slow decline deprives the brain of glucose but fails to trigger the epinephrine response
- symptoms:
- headache
- confusion
- slurred speech
- coma and death
describe insulin injection induced hypoglycemia
- diabetic patients can accidentally inject too much insulin
- activated GLUT-4 lead to glucose uptake into muscle and fat –> hypoglycemia
- mild treated with OJ, juice, carbs
- severe treated with glucagon to stimulate glycogenolysis
describe reactive postprandial hypoglycemia
- exaggerated insulin release following a big meal
- leads to increased uptake of glucose into muscle + fat
- small meals recommended
describe hypoglycemia hepatic genetic diseases
- genetic defects of hepatic enzymes of glycogen degradation and gluconeogenesis lead to reduced release of glucose into the blood during fasting
- abnormal metabolism of dietary fructose and galactose impairs gluconeogenesis
describe alcohol-related fasting hypoglycemia
- common in undernourished, longer fasting or dehydrated individuals after consumption of many drinks with high alc.
- ethanol metabolism in the liver uses NAD+ and forms NADH which leads to an abnormal high NADH/NAD+ ratio
- reduces gluconeogenesis
describe insulinoma
- tumor of the pancreatic islet cells
- over activates GLUT-4 transporters in muscle and fat cells
contrast blood levels of endogenous insulin synthesis vs exogenous insulin synthesis
- endogenous:
- insulin (high)
- C-peptide (high)
- exogenous:
- insulin (high)
- c-peptide (low)
- proinsulin (absent)
how do you diagnose factitious hypoglycemia due to insulin injection
- high levels of insulin
- low levels of C-peptide
- (absence of proinsulin)
- (absence of sulfonylurea)
how do you diagnose factitious hypoglycemia due to sulfonylurea tablet ingestion
sulfonylurea stimulates endogenous insulin synthesis and secretion from pancreas
- high level of insulin
- high level of C-peptide
- presence of proinsulin
- presence of sulfonylurea
