Endocrine Pancreas and Carb Metabolism Flashcards
Active transport of glucose
Occurs in the intestine and kidney
- co transport via Na/glucose
Passive transport of glucose
- GLUT1: fetal tissues, erythrocytes
- GLUT2: renal tubular cells, liver, beta cells
- GLUT3: neruons –> diffusion with high affinity, even at low bg concentrations
- GLUT4: insulin-regulated
Insulin-regulated glucose transport
Present in:
- adipose
- muscle
- heart
- -> inserts into membrane when activated by insulin
GLUT4 is not present in what tissues?
- brain
- liver
Secretions of the endocrine pancreas
Interstitial fluid –> capillaries –> portal vein –> liver –> rest of the body
Insulin structure
Polypeptide
- C peptide: connecting peptide, secreted with insulin and directs fold of insulin
_____ can be used as a marker for endogenous insulin
C-peptide
Insulin structure variations
- dogs: 1 amino acid (same as pigs!)
- cats: 4 amino acids
- horse: 2 amino acids
- cow: 3 amino acids
Insulin is stored in ______
Secretory granules
Insulin in the blood
Circulates mostly unbound
- half life in plasma: 6 min
- mostly cleared within 10-15 min
- degraded by insulinase in liver
- allows rapid turn on/off of insulin functions
Insulin is ______
Anabolic
- decreases bg
- facilitates tissue uptake of glucose, amino acids, fatty acids, K, Mg, P
Insulin stimulates _____
- glycogen synthesis
- lipogenesis
- protein synthesis and storage
Insulin inhibits ______
- glycogenolysis
- lipolysis
- protein catabolism
Insulin receptor binding
Results within seconds!!
- 80% of body’s cells increase glucose uptake (muscle, adipose, NOT most neurons)
- immediate phosphorylation of glucose
Insulin helps transport glucose into the cell, ________ blood glucose
Decreasing
Glucose uptake via GLUT4
Insulin binding –> receptor activation
- translocation of intracellular vesicles with GLUT4 to cell membrane to facilitate glucose uptake into cells
What happens when insulin is no longer available?
Vesicles separate from cell membrane within 3-5 min and move back inside cell until needed again
Insulin is a requirement for glucose transport in all cells in the body, EXCEPT
- neurons
- intestinal epithelium
- renal tubular epithelium
- liver
- RBC
- leukocytes
- beta cells
Insulin binding increases cell membrane permeability to
- amino acids
- K
- P
Slower insulin effect
10-15 minutes
- decrease or increase activity level of intracellular enzymes
- continues for hours to days
Treatment of DKA with IV insulin
- decreases K in blood
- decreases P in blood
- could lead to hemolysis and death
Muscle in the presence of insulin
- absorbs glucose for immediate energy
- synthesizes glycogen for use later
Liver in the presence of insulin
- stimulates glycogenesis (glycogen synthesis)
- inhibits glycogenolysis (glycogen breakdown)
In the absence of insulin (between meals)
- only slightly permeable to glucose
- muscle is dependent on FAs for energy
In the presence of insulin (post-prandial)
- high insulin, bg concentration
- insulin increases permeability to glucose
____ is the preferential energy source during exercise
Glucose
Effects of insulin on liver carbs
Promotes glucose storage in the form of glycogen
Insulin ______ glucose uptake and retention
Enhances
- increases activity of glucokinase (hexokinase)
- decreases activity of phosphatase (would release glucose)
Insulin _____ glycogen synthesis enzymes
Activates
- increases glycogen synthase
- enzyme adds glucose to glycogen polymers
Insulin ______ breakdown of glycogen
Inhibits
- decreases activity of liver phosphorylase
- enzyme causes hepatic glycogen breakdown to glucose
Liver in the absence of insulin (fasting)
Releases glucose into the circulating blood
- decreases bg = decreased pancreatic insulin secretion
- effects of insulin on glucose uptake and glycogen storage is reversed
Glycogen breakdown
Phosphorylase activation
- splits glucose from glycogen
Glucose phosphatase activated (inhibited by insulin)
- allows free glucose to diffuse into blood
Insulin is not present when ________
BG is low
Glucose is the primary energy source in the _____
Brain
- insulin has little effect on uptake/use of glucose in the brain
- critical to maintain BG above a certain level
Promotion of fat synthesis and storage by insulin
- carb excess = promotion of FA synthesis in hepatocytes
- promotes FA transport to and storage in adipose tissue
- inhibits lipolysis (lipid breakdown)
Insulin ____ hepatic glucose uptake
Increases
- increase in hepatic glycogen leads to inhibition of further synthesis
- glucose converted into substrates for FA synthesis via insulin
Insulin ______ lipoprotein lipase
Activates
- splits triglycerides into FA and glycerol
- allows storage of TG in adipose tissue!
Insulin ____ hormone-sensitive lipase
Inhibits
- enzyme causes hydrolysis of TG stored in fat cells
- releases FA from adipose into blood
Insulin deficiency effect on lipids
Causes lipolysis!
- hormone sensitive lipase activation
- hydrolysis of stored TG = release of FA and glycerol into blood –> ketone formation in liver –> conversion of some FA into phospholipids and cholesterol
Insulin ______ protein synthesis and storage
Promotes
- stimulates transport of amino acids into cells, increasing translation of mRNA
- inhibits protein catabolism
- decreases hepatic gluconeogenesis
Hypoglycemia
Brain depends upon a constant blood glucose concentration for optimal function
Hyperglycemia
Causes decreased osmotic pressure and cellular dehydration
- loss of glucose in urine results in osmotic diuresis and dehydration
- damage to blood vessels and nerves over time (humans)
The _____ is the primary regulator of insulin release
Blood glucose
- glucose enters beta cells via GLUT 2 (non-insulin dependent)
- rate of glucose entry controls exocytosis of insulin vesicles
High BG = ____ insulin secretion
Increase
Low BG = ____ insulin secretion
Decrease
Stimuli of insulin secretion
- increased blood amino acids
- increased blood FAs
- GI hormones
- parasympathetic stimulation
- GH, cortisol, glucagon, etc
Inhibition of insulin release
- somatostatin
- sympathetic activity
- fasting
Glucagon function
Anti-insulin/diabetogenic
- rapid acting
- hepatic glycogenolysis
- hepatic glucogenesis (amino acid mobilization)
- lipolysis
Glucagon regulation in response to glucose
- decrease glucose = increased glucagon secretion
- increase glucose = decreased glucagon secretion
Amino acids ____ glucagon secretion
Stimulate
- same as insulin!!
- for gluconeogenesis
