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Glucagon Diabetes mellitus Islet microcirculation

Glucagon Diabetes mellitus Islet microcirculation

Glucagon Diabetes mellitus Islet microcirculation

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Isolated α-cell<br />

• Insulin receptor transcript was relatively abundant in α-<br />

cells, similar to liver<br />

α-Cells are also important sites of insulin action<br />

• Transcript for GLP-1 receptor was not detected in α-cells<br />

nor did GLP-1 stimulate α-cell glucagon release<br />

in agreement with earlier studies:<br />

– cAMP levels in α-cells were unaffected by GLP-1<br />

– type 1 DM : GLP-1 had no effect on plasma glucagon levels<br />

during hyperinsulinemic-euglycemic clamp<br />

• Apparent direct inhibition by GLP-1 on glucagon secretion<br />

: paracrine factors may have mediated the suppression<br />

43<br />

44<br />

<strong>Glucagon</strong> secretion from in situ–perfused rat pancreas<br />

Membrane potential recording from an isolated α-cell<br />

using the perforated-patch whole-cell configuration<br />

Data are mean+SE of six independent perfusions<br />

45<br />

The recording is typical of six cells.<br />

46<br />

Electrical activity in response to “Zn-free" insulin was<br />

analyzed and the effect on spike frequency calculated<br />

<strong>Glucagon</strong> secretion from isolated α-cells<br />

Data are mean+ SE of six experiments<br />

47<br />

mean+SE *P < 0.05, **P < 0.005<br />

48

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