Context: Insulin resistance impacts virtually all tissues, incluDing pancreatic cells. Individuals with insulin resistance, but without diabetes, exhibit an increased islet size because of an elevated number of both and cells. Neogenesis from duct cells and transdifferentiation of cells have been postulated to contribute to the α-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 α-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), α-Cell glucose sensitivity was unique in exhibiting a significant correlation with both islet size and-double islet cells. Conclusions: Our data suggest that poor α-Cell glucose sensitivity is linked to islet transdifferentiation, possibly from cells to 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 α-Cell mass for diabetes therapy.

Mezza, T., Sorice, G. P., Conte, C., Sun, V. A., Cefalo, C. M. A., Moffa, S., Pontecorvi, A., Mari, A., Kulkarni, R. N., Giaccari, A., β α-Cell glucose sensitivity is linked to insulin/glucagon bihormonal cells in nondiabetic humans, <<THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM>>, N/A; 101 (2): 470-475. [doi:10.1210/jc.2015-2802] [http://hdl.handle.net/10807/94096]

β α-Cell glucose sensitivity is linked to insulin/glucagon bihormonal cells in nondiabetic humans

Mezza, Teresa
Primo
;
Conte, Caterina;Sun, Vinsin Alice;Cefalo, Chiara Maria Assunta;Moffa, Simona;Pontecorvi, Alfredo;Giaccari, Andrea
2016

Abstract

Context: Insulin resistance impacts virtually all tissues, incluDing pancreatic cells. Individuals with insulin resistance, but without diabetes, exhibit an increased islet size because of an elevated number of both and cells. Neogenesis from duct cells and transdifferentiation of cells have been postulated to contribute to the α-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 α-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), α-Cell glucose sensitivity was unique in exhibiting a significant correlation with both islet size and-double islet cells. Conclusions: Our data suggest that poor α-Cell glucose sensitivity is linked to islet transdifferentiation, possibly from cells to 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 α-Cell mass for diabetes therapy.
Inglese
Mezza, T., Sorice, G. P., Conte, C., Sun, V. A., Cefalo, C. M. A., Moffa, S., Pontecorvi, A., Mari, A., Kulkarni, R. N., Giaccari, A., β α-Cell glucose sensitivity is linked to insulin/glucagon bihormonal cells in nondiabetic humans, <<THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM>>, N/A; 101 (2): 470-475. [doi:10.1210/jc.2015-2802] [http://hdl.handle.net/10807/94096]
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