Context: Insulin resistance impacts virtually all tissues, including pancreatic β cells. Individuals with insulin resistance, but without diabetes, exhibit an increased islet size because of an elevated number of both β and α cells. Neogenesis from duct cells and transdifferentiation of α cells have been postulated to contribute to the β-cell compensatory response to insulin resistance. Objective: Our objective was to explore parameters that could potentially predict altered islet morphology. Methods: We investigated 16 nondiabetic subjects by a 2-hour hyperglycemic clamp to evaluate β-cell secretory function. We analyzed pancreas samples obtained during pancreatoduodenectomy in the same patients to examine glucagon and insulin double+ cells to assess islet morphology. Results: Among all the functional in vivo parameters of insulin secretion that were explored (basal, first phase and total secretion, glucose sensitivity, arginine-stimulated insulin secretion), β-cell glucose sensitivity was unique in exhibiting a significant correlation with both islet size and α-β double+ islet cells. Conclusions: Our data suggest that poor β-cell glucose sensitivity is linked to islet transdifferentiation, possibly from α cells to β cells, in an attempt to cope with higher demands for insulin secretion. Understanding the mechanism(s) that underlies the adaptive response of the islet cells to insulin resistance is a potential approach to design tools to enhance functional β-cell mass for diabetes therapy.

Mezza, T., Sorice, G., Conte, C., Sun, V. A., Cefalo, C. M. A., Moffa, S., Pontecorvi, A., Mari, A., Kulkarni,, Giaccari, A., β-Cell Glucose Sensitivity Is Linked to Insulin/Glucagon Bihormonal Cells in Nondiabetic Humans., <<THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM>>, 2016; Volume 101 (Febbraio): 470-475. [doi:10.1210/jc.2015-2802] [http://hdl.handle.net/10807/71735]

β-Cell Glucose Sensitivity Is Linked to Insulin/Glucagon Bihormonal Cells in Nondiabetic Humans.

Mezza, Teresa;Sorice, Gianpio;Conte, Caterina;Sun, Vinsin Alice;Cefalo, Chiara Maria Assunta;Moffa, Simona;Pontecorvi, Alfredo;Giaccari, Andrea
2015

Abstract

Context: Insulin resistance impacts virtually all tissues, including pancreatic β cells. Individuals with insulin resistance, but without diabetes, exhibit an increased islet size because of an elevated number of both β and α cells. Neogenesis from duct cells and transdifferentiation of α cells have been postulated to contribute to the β-cell compensatory response to insulin resistance. Objective: Our objective was to explore parameters that could potentially predict altered islet morphology. Methods: We investigated 16 nondiabetic subjects by a 2-hour hyperglycemic clamp to evaluate β-cell secretory function. We analyzed pancreas samples obtained during pancreatoduodenectomy in the same patients to examine glucagon and insulin double+ cells to assess islet morphology. Results: Among all the functional in vivo parameters of insulin secretion that were explored (basal, first phase and total secretion, glucose sensitivity, arginine-stimulated insulin secretion), β-cell glucose sensitivity was unique in exhibiting a significant correlation with both islet size and α-β double+ islet cells. Conclusions: Our data suggest that poor β-cell glucose sensitivity is linked to islet transdifferentiation, possibly from α cells to β cells, in an attempt to cope with higher demands for insulin secretion. Understanding the mechanism(s) that underlies the adaptive response of the islet cells to insulin resistance is a potential approach to design tools to enhance functional β-cell mass for diabetes therapy.
Inglese
Mezza, T., Sorice, G., Conte, C., Sun, V. A., Cefalo, C. M. A., Moffa, S., Pontecorvi, A., Mari, A., Kulkarni,, Giaccari, A., β-Cell Glucose Sensitivity Is Linked to Insulin/Glucagon Bihormonal Cells in Nondiabetic Humans., <>, 2016; Volume 101 (Febbraio): 470-475. [doi:10.1210/jc.2015-2802] [http://hdl.handle.net/10807/71735]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/71735
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