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35 Cards in this Set

  • Front
  • Back
metabolic homeostastis is achieved via
1) concentration of nutrients/metabolites in blood affect rate of use/storage by tissues 2) hormones carry messages 3) CNS uses neural signals to control tissue metabolism (directly or via hormones)
what is the minimum required glucose in a day
190 g - 140 for brain and 40 for other tissues
decrease of blood glucose below what level limits brain glucose metabolism
<60 mg/dL; dur to Km values of glucose transporters required
glucagon sites of action
liver and adipose tissue (muscle cells lack glucagon receptors)
when do highest levels of insulin occur
30-45 minutes after a high carb meal; return to basal levels ~120 minutes after meal
what is the release of cortisol, epinephrine, and norepi mediated by? How about insulin and glucagon?
neuronal signals; glucose concentration
elevated epi levels cause
tachycardia, palpitations, anxiety, tremulousness, pallor, and sweating
hypoglycemic symptoms
fatigue, confusion, blurred vision
insulin structure
2 polypeptide chains linked by two interchain disulfide bonds
formation of insulin
preprohormone converted to prohormone in RER; microvesicles to golgi - storage vesicles have protease that removes the C-peptide forming insulin
zinc and insulin
zinc is transported into insulin storage vesicles; once C-peptide removed insulin is less soluble and co-precipitates with Zinc
transporters in B-cells that allow glucose entry
GLUT-2
what forms glucose 6-phosphate
glucose phosphorylation via glucokinase
What happens in B-cells as ATP/ADP ratio increases
activity of membrane-bound ATP-dependent K+ channel is inhibited causing membrane depolarization
genetic susceptability to diabetes type I
human leukocyte antigen (HLA) region of B-cels that codes for the major histocompatibility complex II (MHC II)
threshold for insulin release
80 mg/dL
what gastric hormones aid in insulin release
GIP and GLP-1
MODY mutations
in glucokinase or specific nuclear transcription factors
most common mutation leading to permanent neonatal diabetes
KCNJ11 which encodes a subunit of the K+ channel in various tissues
glipizide
sulfonylurea drug; act on K+ channels of B-cells - bind and inactivate causing insulin release
direction of blood flow in the pancreas importance
carries insulin from B-cells in center of islets to peripheral a-bells where it supresses glucagon secretion
why would aas stimulate glucagon and insulin secretion (like after a high protein meal)
insulin stimulate uptake and protein synthesis, glucagon stimulates gluconeogenesis
wha provides an acurate estimate of insulin secretion rate
C-peptide - secreted in equal amounts as insulin, but not cleared as quickly
3 basic types of signal transduction for hormones binding to receptors on the plasma membrane
1) receptor coupled adenylyl cyclase 2) receptor kinase activity 3) receptor coupled hydrolysis of PIP2
insulin receptor
2 alpha, 2 beta subunits; cytosolic B has tyrosine kinase activity
principle substrate of insulin receptor phosphorylation
insulin-receptor substrate-1 (IRS-1)
5 basic tissue responses to insulin
1) reverses glucagon-stimulated phosphorylation 2) cascade to activate several enzymes 3) induces and represses synthesis of specific enzymes 4) GF and stimulatory effect on protein synthesis 5) stimulates glucose and aa transport into cells
in diabetes type I and II, what other hormone besides insulin has a change in concentration
glucagon - normally inhibited by insulin
glucagon signaling cascade
adenylyl cyclase to cAMP via G proteins to protein kinase A to enzyme phosphorylation (at specific serine residues)
3 beta-adrenergic receptors
work via adenylate cyclase-cAMP system
B1 receptor
major adrenergic receptor in the heart; primarily stimulated by norepi
B2-receptor
liver, skeletal muscle, and other tissues; mobilization of fuels, mediates vasculat, bronchial, and uterine smooth muscle contraction; epi>norepi
a3-receptor
mostly adipose tissue, some skeletal muscle; stimulates fatty acid oxidation and thermogenesis
one of most important cellular responses to insulin
reversal of glucagon-stimulated phosphorylation of enzymes
phosphoenolpyruvate carboxykinase
key enzyme of gluconeogenic pathway; increased by glucagon, decreased by insulin