β-Cell Glucose Sensitivity Is Linked to Insulin/Glucagon Bihormonal Cells in Nondiabetic Humans
| Autor: | Andrea Mari, Simona Moffa, Chiara Maria Assunta Cefalo, Caterina Conte, Andrea Giaccari, Gian P. Sorice, Rohit N. Kulkarni, Alfredo Pontecorvi, Teresa Mezza, Vinsin A. Sun |
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| Přispěvatelé: | Mezza, T, Sorice, Gp, Conte, C, Sun, Va, Cefalo, Cm, Moffa, S, Pontecorvi, A, Mari, A, Kulkarni, Rn, Giaccari, A |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Biochemistry 0302 clinical medicine Endocrinology insulin resistance Insulin-Secreting Cells Insulin geography.geographical_feature_category Chemistry Glucose clamp technique Middle Aged Islet Insulin oscillation Diabetes and Metabolism Female Hyperglycemic agent Adult medicine.medical_specialty trans-differentiation 030209 endocrinology & metabolism Glucagon Aged Glucose Glucose Clamp Technique Humans Hyperglycemia Hyperinsulinism Islets of Langerhans Pancreas Pancreatic Ducts Pancreatic Function Tests Pancreaticoduodenectomy Biochemistry (medical) 03 medical and health sciences β-cell glucose sensitivity Insulin resistance Internal medicine medicine geography Settore MED/13 - ENDOCRINOLOGIA Original Articles medicine.disease 030104 developmental biology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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