| First Author | Boland BB | Year | 2019 |
| Journal | Diabetes | Volume | 68 |
| Issue | 1 | Pages | 131-140 |
| PubMed ID | 30305366 | Mgi Jnum | J:268250 |
| Mgi Id | MGI:6269193 | Doi | 10.2337/db18-0304 |
| Citation | Boland BB, et al. (2019) Pancreatic beta-Cell Rest Replenishes Insulin Secretory Capacity and Attenuates Diabetes in an Extreme Model of Obese Type 2 Diabetes. Diabetes 68(1):131-140 |
| abstractText | The onset of common obesity-linked type 2 diabetes (T2D) is marked by exhaustive failure of pancreatic beta-cell functional mass to compensate for insulin resistance and increased metabolic demand, leading to uncontrolled hyperglycemia. Here, the beta-cell-deficient obese hyperglycemic/hyperinsulinemic KS db/db mouse model was used to assess consequential effects on beta-cell functional recovery by lowering glucose homeostasis and/or improving insulin sensitivity after treatment with thiazolidinedione therapy or glucagon-like peptide 1 receptor agonism alone or in combination with sodium/glucose cotransporter 2 inhibition (SGLT-2i). SGLT-2i combination therapies improved glucose homeostasis, independent of changes in body weight, resulting in a synergistic increase in pancreatic insulin content marked by significant recovery of the beta-cell mature insulin secretory population but with limited changes in beta-cell mass and no indication of beta-cell dedifferentiation. Restoration of beta-cell insulin secretory capacity also restored biphasic insulin secretion. These data emphasize that by therapeutically alleviating the demand for insulin in vivo, irrespective of weight loss, endogenous beta-cells recover significant function that can contribute to attenuating diabetes. Thus, this study provides evidence that alleviation of metabolic demand on the beta-cell, rather than targeting the beta-cell itself, could be effective in delaying the progression of T2D. |
