| First Author | Huang YC | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 2 | Pages | 519-30 |
| PubMed ID | 23043159 | Mgi Jnum | J:208468 |
| Mgi Id | MGI:5563587 | Doi | 10.2337/db11-0786 |
| Citation | Huang YC, et al. (2013) In situ electrophysiological examination of pancreatic alpha cells in the streptozotocin-induced diabetes model, revealing the cellular basis of glucagon hypersecretion. Diabetes 62(2):519-30 |
| abstractText | Early-stage type 1 diabetes (T1D) exhibits hyperglucagonemia by undefined cellular mechanisms. Here we characterized alpha-cell voltage-gated ion channels in a streptozotocin (STZ)-induced diabetes model that lead to increased glucagon secretion mimicking T1D. GYY mice expressing enhanced yellow fluorescence protein in alpha cells were used to identify alpha cells within pancreas slices. Mice treated with low-dose STZ exhibited hyperglucagonemia, hyperglycemia, and glucose intolerance, with 71% reduction of beta-cell mass. Although alpha-cell mass of STZ-treated mice remained unchanged, total pancreatic glucagon content was elevated, coinciding with increase in size of glucagon granules. Pancreas tissue slices enabled in situ examination of alpha-cell electrophysiology. alpha cells of STZ-treated mice exhibited the following: 1) increased exocytosis (serial depolarization-induced capacitance), 2) enhanced voltage-gated Na(+) current density, 3) reduced voltage-gated K(+) current density, and 4) increased action potential (AP) amplitude and firing frequency. Hyperglucagonemia in STZ-induced diabetes is thus likely due to increased glucagon content arising from enlarged glucagon granules and increased AP firing frequency and amplitude coinciding with enhanced Na(+) and reduced K(+) currents. These alterations may prime alpha cells in STZ-treated mice for more glucagon release per cell in response to low glucose stimulation. Thus, our study provides the first insight that STZ treatment sensitizes release mechanisms of alpha cells. |
