Amylin modulates beta-cell glucose sensing via effects on stimulus-secretion coupling.
The release of insulin from the pancreatic beta cell is dependent upon a complex interplay between stimulators and inhibitors. Recently, amylin, a peptide secreted by pancreatic beta cells, has been implicated in the development of type II (noninsulin dependent) diabetes through its modulation of the peripheral effects of insulin. However, the effect of amylin on insulin secretion from the beta cell has remained controversial. It is reported here that in single beta cells exhibiting normal glucose sensing, amylin causes membrane hyperpolarization, increases in net outward current, and reductions in insulin secretion. In contrast, in cells with abnormal glucose sensing (e.g., from db/db diabetic mice), amylin has no effect on electrical activity or secretion. Thus, amylin's effects on excitation-secretion coupling in the beta cell of the pancreas appear to be linked to the cell's capacity for normal glucose sensing.
Wagoner
P K
PK
Department of Cell Physiology and Biophysics, Glaxo Research Institute, Glaxo, Inc., Research Triangle Park, NC 27709.
Chen
C
C
Worley
J F
JF
Dukes
I D
ID
Oxford
G S
GS
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D002463:Cell Membrane Permeability; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000503:physiopathology; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009761:Nystatin; D010190:Pancreatic Neoplasms; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D009761:Nystatin; D005947:Glucose