Abstract
BackgroundThe mass of pancreatic β-cells varies according to increases in insulin demand. It is hypothesized that functionally heterogeneous β-cell subpopulations take part in this process. Here we characterized two functionally distinct groups of β-cells and investigated their physiological relevance in increased insulin demand conditions in rats.MethodsTwo rat β-cell populations were sorted by FACS according to their PSA-NCAM surface expression, i.e. βhigh and βlow-cells. Insulin release, Ca2+ movements, ATP and cAMP contents in response to various secretagogues were analyzed. Gene expression profiles and exocytosis machinery were also investigated. In a second part, βhigh and βlow-cell distribution and functionality were investigated in animal models with decreased or increased β-cell function: the Zucker Diabetic Fatty rat and the 48 h glucose-infused rat.ResultsWe show that β-cells are heterogeneous for PSA-NCAM in rat pancreas. Unlike βlow-cells, βhigh-cells express functional β-cell markers and are highly responsive to various insulin secretagogues. Whereas βlow-cells represent the main population in diabetic pancreas, an increase in βhigh-cells is associated with gain of function that follows sustained glucose overload.ConclusionOur data show that a functional heterogeneity of β-cells, assessed by PSA-NCAM surface expression, exists in vivo. These findings pinpoint new target populations involved in endocrine pancreas plasticity and in β-cell defects in type 2 diabetes.
Highlights
Pancreatic b-cells synthesize and release insulin with a remarkable degree of plasticity over time that allows adaptation to the metabolic environment
Pancreatic b-cells are heterogeneous for PSA-NCAM Staining of rat pancreas for PSA-NCAM and insulin showed that PSA-NCAM was exclusively located in islets and was not expressed in the exocrine tissue (Fig. 1A)
B-cells expressed different levels of PSA-NCAM, i.e. they were heterogeneous for PSA-NCAM expression
Summary
Pancreatic b-cells synthesize and release insulin with a remarkable degree of plasticity over time that allows adaptation to the metabolic environment. This involves increased b-cell function, i.e. an increase both in insulin production and secretion as well as enlargement of the b-cell pool [1]. Insulin resistance as part of pregnancy or obesity is compensated via an increase in both b-cell number and responsiveness to glucose. This mechanism allows the maintenance of euglycemia in spite of decreased insulin sensitivity [3,4]. We characterized two functionally distinct groups of b-cells and investigated their physiological relevance in increased insulin demand conditions in rats
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