Dynamics of insulin secretion and the clinical implications for obesity and diabetes
Susumu Seino, Tadao Shibasaki, Kohtaro Minami
Susumu Seino, Tadao Shibasaki, Kohtaro Minami
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Dynamics of insulin secretion and the clinical implications for obesity and diabetes

Abstract

Insulin secretion is a highly dynamic process regulated by various factors including nutrients, hormones, and neuronal inputs. The dynamics of insulin secretion can be studied at different levels: the single β cell, pancreatic islet, whole pancreas, and the intact organism. Studies have begun to analyze cellular and molecular mechanisms underlying dynamics of insulin secretion. This review focuses on our current understanding of the dynamics of insulin secretion in vitro and in vivo and discusses their clinical relevance.

Authors

Susumu Seino, Tadao Shibasaki, Kohtaro Minami

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Figure 2

Existing and new models of GSIS in the normal state.

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Existing and new models of GSIS in the normal state. (A) In the existing...
(A) In the existing model of GSIS, the first phase of insulin secretion results from a RRP composed of docked insulin granules (old face); the second phase of secretion results from a RP composed of granules located farther away (resting newcomer) that are newly recruited upon stimulation, docked, and fused to the plasma membrane. (B) In the new model, both phases consist of insulin granules that are recruited upon stimulation and immediately fused to the plasma membrane (restless newcomer). A RRP responsible for the first phase is located more than 50 nm from the plasma membrane, yet is immediately releasable. The second phase of insulin secretion involves exocytosis of insulin granules from a RP associated with the cortical actin network regulated by glucose-evoked signals in a mechanism yet to be elucidated.