Glucose Homeostasis

imissyou419's version from 2017-04-01 17:49


Question Answer
Hypoglycemic actioninsulin - decrease plasma glucose (insulin makes you hypoglycemic)
Hyperglycemic actionglucagon, epinephrine, cortisol, GH - increases plasma glucose
What is the best source for the generation of cellular ATP?glucose
Where in ATP is the energy for all cellular processes stored?3rd phosphate bond of ATP, most activites in cell regulated by phosphorylation
Glycolysisconvert glucose (C6) to pyruvate or lactate (C3) and produces 2 ATP
TCA cycleusing acetyl coA, produces 2 ATP
ETCin mitochondrial membranes, produces 34 ATP
The 3 steps in glucose breakdown produce how much total ATP38 ATP/molecule glucose
GLUT1Brain, erythrocytes, placenta, fetal tissue; Low Km (high affinity transporter) - constant uptake of glucose
GLUT2 KNOW THISLiver, kidney, intestine, pancreatic beta-cells; High Km (low affinity) - glucose equilibration across membrane
GLUT3Brain; Low Km - preferential uptake in hypoglycemia
GLUT4 KNOW THISMuscle and adipose; Med Km - insulin-sensitive (GLUT4 translocated from cytosol to PM after a meal when insulin released from pancreatic beta-cells through GLUT2)
GLUT5Jejunum; Med Km - fructose uptake
Pancreas exocrine cells calledacinar cells - secrete enzymes involved in breaking down food, makes up most of pancreas
alpha-cells in Islets of Langerhans produceglucagon (periphery)
beta-cells in Islets of Langerhans produceinsulin and amyloid (too much is toxic to beta cell)
delta-cells in Islets of Langerhans producesomatostatin (important with respect to GH release)
D1 cells in Islets of Langerhans produceVIP (water and electrolyte balance)
PP cells in Islets of Langerhans producepancreatic polypeptide (metabolism and digestion)
Insulin biosynthesisPreproinsulin is made in ER, signal peptidase removes N terminus signal sequence, becomes proinsulin
In Golgi, Endopeptidase cleaves C-chain, Exopeptidase, carboxypeptidase cleans up C-termini, placed in secretory vesicles (stored and released in quick matter resp for 1st phase)
Insulin secretion biphasic response1st peak within 1-5 mins of glucose load "meal",
2nd peak 15-20+ mins
Phase 1: release of stored insulin (1-5 min spike)1. glucose enters beta-cells via GLUT2,
2. increase glucose metabolism closes ATP-regulated K+ channels,
3. depolarization opens VG-Ca2+ channels,
4. Ca2+ mediated release of stored insulin
Phase 2: autocrine action of insulinBoth increased intracellular Ca2+ and secreted insulin increase insulin transcription;
- increased intracellular Ca2+ activates CaM kinase which increase insulin gene transcription;
- secreted insulin bind to insulin tyrosine kinase receptor, phosphorylation activates IRS-1 (insulin receptor substrate-1), IRS-1 activates PI-3 kinase, activate p70, which increase transcription of insulin gene (in adipose or muscle tissues, activation of insulin receptor activates IRS-1, PI3 kinase leading to translocation of GLUT4 to PM)
Tyrosine Kinase Receptorsreceptors for PDGF, NGF, Insulin, FGF, VEGF; 2 monodimers dimerize when insulin binds, receptor activation and downstream signalling
Signal terminationreceptor dephosphorylation (phosphatases activated by signal cascade),
Ca2+ pumps (return Ca2+ to ER and ECF),
phosphodisterase (inactivates GTP - for MAPK),
transcription factor dephosphorylation
Insulin receptor functionincrease growth, prosurvivial, proproliferative (there is a lot of nutrients, i can flourish), translocation of GLUT4 in adipose and muscle cells
Insulin functionInsulin stimulates glucose intake via GLUT4 in muscle and adipsoe and energy metabolism (make ATP); promotes energy utilization and storage:
increase glycogenesis, triglyceride synthesis in liver;
increase glucose, a.a. intake, glycogenesis, protein synthesis in muscle;
increase free fatty and acid glucose uptake, triglyceride synthesis and lipogenesis, leptin transcription and secretion in adipose;
decrease hunger in brain (insulin and leptin action)
Glucose -> triglyceride in adipose convert byPPARgamma (PPARgamma knock out mice can't store gain adipose tissue)
When insulin binds to insulin receptor in the liver, what happens?glucose -> glycogen but also some glycogen -> glucose
In fasting stateprotein -> amino acid in muscle, triglycerides -> fatty acid in adipose tissue, liver takes a.a. and fatty acids and makes glucose/ketone bodies, liver also makes glucose from glycogen
Adipo-insular axisInsulin act on adipose tissue to make leptin, leptin produced shuts down synthesis of insulin;
leptin and insulin act on the brain to decrease hunger (leptin also increases energy utilization);
sympathetic stimulating on pancreas shuts down insulin production (brain wants high glucose), parasympathetic stimulation drives insulin production
Glucagon29 a.a peptide hormone, pancreatic alpha-beta cells (periphery cells of islets of Langerhans), GlucR is GPCR linked to Gsalpha
Glucagon actionsopposes insulin, increase glycogenolysis and gluconeogenesis in liver, lipolysis in fat which increase glycerol and FFA for tisuse/muscle metabolism, increase a.a transport (muscle breakdown) for liver gluconeogenesis
Glucagon stimulated byfall in blood glucose, high circulating a.a. and increased CCK from GI tract (saying eating a lot of protein, not carbs)
Does glucagon have a direct link to leptin function?No (insulin does but glucagon does not)
Direct and indirect glucagon controlDirect - SNS release NE acts on alpha-islets cells to provide glucagon, glucagon act on liver to increase glucose;
Indirect - splachnic nerves innervate adrenal medulla produce E, act on alpha-islets cells to further increase glucagon production, direct effect on liver cells to increase gluconeogenesis
How is circulating glucose maintained overnight?Not due to glucagon (it is decreasing at night), due to the surge of circulating cortisol and GH during night, liver increasing gluconeogenesis via activation of PEPCK, G6Pase, these surge of hormones also decrease glucose uptake in tissue
Incretins released when, action, deactivated bysmall peptides released from gut cells in response to glucose (meal),
GLP-1 = glucagon-like peptide-1 released by L-cells, GIP = glucose-dependent insulinotropic peptide released by K-cells in response to stretch, bind to receptors in pancreas and prime pancreas to make insulin (make insulin in absence of high glucose);
Incretin augment insulin response to oral glucose (need stretch of stomach leading to increased insulin)
GLP-1 bind to its receptor -> increase cAMP -> Ca2+ from ER freed so enhance insulin secretion
Many drugs target GLP receptor to increase insulin secretion
incretins rapidly deactivated by serum enzyme, dipeptidyl-peptidase 4 (DPP-4)

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