| First Author | Kaihara KA | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 5 | Pages | 1527-36 |
| PubMed ID | 23349500 | Mgi Jnum | J:208561 |
| Mgi Id | MGI:5563711 | Doi | 10.2337/db12-1013 |
| Citation | Kaihara KA, et al. (2013) beta-Cell-specific protein kinase A activation enhances the efficiency of glucose control by increasing acute-phase insulin secretion. Diabetes 62(5):1527-36 |
| abstractText | Acute insulin secretion determines the efficiency of glucose clearance. Moreover, impaired acute insulin release is characteristic of reduced glucose control in the prediabetic state. Incretin hormones, which increase beta-cell cAMP, restore acute-phase insulin secretion and improve glucose control. To determine the physiological role of the cAMP-dependent protein kinase (PKA), a mouse model was developed to increase PKA activity specifically in the pancreatic beta-cells. In response to sustained hyperglycemia, PKA activity potentiated both acute and sustained insulin release. In contrast, a glucose bolus enhanced acute-phase insulin secretion alone. Acute-phase insulin secretion was increased 3.5-fold, reducing circulating glucose to 58% of levels in controls. Exendin-4 increased acute-phase insulin release to a similar degree as PKA activation. However, incretins did not augment the effects of PKA on acute-phase insulin secretion, consistent with incretins acting primarily via PKA to potentiate acute-phase insulin secretion. Intracellular calcium signaling was unaffected by PKA activation, suggesting that the effects of PKA on acute-phase insulin secretion are mediated by the phosphorylation of proteins involved in beta-cell exocytosis. Thus, beta-cell PKA activity transduces the cAMP signal to dramatically increase acute-phase insulin secretion, thereby enhancing the efficiency of insulin to control circulating glucose. |
