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