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Desensitization of the insulin‐secreting beta cell
Author(s) -
Grodsky Gerold M.,
Bolaffi Janice L.
Publication year - 1992
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240480103
Subject(s) - desensitization (medicine) , endocrinology , insulin , medicine , potentiator , stimulation , secretion , basal (medicine) , carbohydrate metabolism , beta cell , diabetes mellitus , biology , receptor , pharmacology , islet
In human diabetes, inherent impaired insulin secretion can be exacerbated by desensitization of the β cell by chronic hyperglycemia. Interest in this phenomenon has generated extensive studies in genetic or experimentally induced diabetes in animals and in fully in vitro systems, with often conflicting results. In general, although chronic glucose causes decreased β‐cell response to this carbohydrate, basal response and response to alternate stimulating agents are enhanced. Glucose‐stimulated insulin synthesis can be increased or decreased depending on the system studied. Using a two‐compartment β‐cell model of phasic insulin secretion, a unifying hypothesis is described which can explain some of the apparent conflicting data. This hypothesis suggests that glucose‐desensitization is caused by an impairment in stimulation of a hypothetical potentiator singularly responsible for: (1) some of the characteristic phases of insulin secretion; (2) basal release; (3) potentiation of non‐glucose stimulators; and (4) apparent “recovery” from desensitization. Review of some of the pathways that regulate insulin secretion suggest that phosphoinositol metabolism and protein kinase‐C production are regulated similarly to the theoretical potentiator and their impairment is a major contributor to glucose desensitization in the β cell.