TY - JOUR
T1 - β-Cell Glucose Sensitivity Is Linked to Insulin/Glucagon Bihormonal Cells in Nondiabetic Humans.
AU - Mezza, Teresa
AU - Sorice, Gianpio
AU - Conte, Caterina
AU - Sun, Vinsin Alice
AU - Cefalo, Chiara Maria Assunta
AU - Moffa, Simona
AU - Pontecorvi, Alfredo
AU - Mari, Andrea
AU - Kulkarni, Rohit N.
AU - Giaccari, Andrea
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - insulin resistance
KW - trans-differentiation
KW - β-cell glucose sensitivity
KW - insulin resistance
KW - trans-differentiation
KW - β-cell glucose sensitivity
UR - http://hdl.handle.net/10807/71735
U2 - 10.1210/jc.2015-2802
DO - 10.1210/jc.2015-2802
M3 - Article
SN - 1945-7197
VL - 101
SP - 470
EP - 475
JO - THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
JF - THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
ER -