BCHS-4361-09-DIABETE_38364

When atp is produced the adpatp ratio falls and the

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When ATP is produced, the ADP/ATP ratio falls and the ATP- sensitive potassium channel (K ATP ) closes. This depolarizes the plasma membrane and opens a voltage-dependent calcium channel, allowing Ca 2+ to enter and accumulate in the cytoplasm. Its concentration rises 100x from 100 nM to 10 μ M. This change leads to increased insulin secretion in what is called the first or rapid phase. Lasts only a few minutes and releases preformed and readily mobilized insulin..
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II. INSULIN SECRETION BY THE β CELL A second phase of insulin secretion occurs after a delay and lasts much longer. It releases both preformed and newly synthesized hormone. Insulin secretion in this phase appears to require cyclic AMP. In the secretory process, insulin-containing granules move from cytoplasm to plasma membrane via microtubules. A microfilament system aids in emptying the granules and releasing insulin via exocytosis.
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Glucose 1 G L U T 2 ATP METABOLISM 2 Ca 2+ Protein kinase A INSULIN BIOSYNTHESIS AND PROCESSING cAMP AC Protein kinase C DAG Figure 4. Control of insulin synthesis and secretion by glucose Ca 2+ 3 CaM-kinase IMMEDIATE SECRETION 5 Ca 2 + - mitos 4 Calmodulin 6 8 7 9 9
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III. INSULIN SECRETION BY THE β CELL The rate limiting step is phosphorylation of glucose to glucose-6-P by glucokinase (K m for glucose=5-10 mM) . Hence glucokinase is considered to be the glucose sensor. A partial decrease in glucokinase causes diabetes, thereby implicating this enzyme as a “gatekeeper” in maintaining the insulin supply. Also, the age-dependent decline in mitochondrial oxidative capacity may be related to age-dependent onset of NIDDM. Possibly, overproduction of insulin in NIDDM reflects inability of aged cells to properly regulate insulin production.
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Extracellular Cytoplasm 1 insulin binds L R 2 IRTK (L) activated OP OP 3 IRTK (R) phosphorylated/ activated Figure 3. Activation of the tyrosine kinase domains of the insulin receptor by insulin binding, followed by interchain autophosphorylation P P P P ATPs ADPs Phosphorylation catalyzed by IRTK (L) P
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Extracellular Cytoplasm 1 insulin binds L R 2 IRTK (L) activated OP OP 3 IRTK (R) phosphorylated/ activated PO PO 4 IRTK (L) phosphorylated OP OP Figure 3. Activation of the tyrosine kinase domains of the insulin receptor by insulin binding, followed by interchain autophosphorylation P P P P ATPs ADPs Phosphorylation catalyzed by IRTK (L) ATPs ADPs P P
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I. INSULIN ACTION Prevailing [insulin]=10 -10 M. The hormone has major effects on lipid, protein and CHO metabolism in insulin-sensitive tissues. One aspect is to increase insulin uptake, especially in muscle and fat cells. The major glucose transporter in these tissues is GLUT4. At rest, GLUT4 transporters are sequestered at sites in the cytoplasm. When insulin bins to receptor, translocation of transporter to plasma membrane occurs and increases capacity for glucose uptake.
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