In Situ Electrophysiological Examination of Pancreatic α Cells in the Streptozotocin-Induced Diabetes Model, Revealing the Cellular Basis of Glucagon Hypersecretion
| Autor: | Pedro Luis Herrera, Negar Karimian, Patrick Gilon, Ya-Chi Huang, Marjan Slak Rupnik, Herbert Y. Gaisano, Zhong-Ping Feng |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Action Potentials/physiology
endocrine system diseases Endocrinology Diabetes and Metabolism Hyperglycemia/blood/physiopathology Action Potentials Stimulation Voltage-Gated Sodium Channels Glucagon-Secreting Cells/pathology/physiology Mice 0302 clinical medicine Exocytosis/physiology ddc:576.5 Cells Cultured 0303 health sciences Chemistry Potassium channel medicine.anatomical_structure Diabetes Mellitus Experimental/physiopathology Potassium Channels Voltage-Gated Pancreas medicine.drug medicine.medical_specialty Potassium Channels Voltage-Gated/physiology Glucagon/analysis/blood/secretion 030209 endocrinology & metabolism Glucagon Exocytosis Diabetes Mellitus Experimental Glucose Intolerance/physiopathology 03 medical and health sciences Diabetes Mellitus Type 1/chemically induced/physiopathology Diabetes mellitus Internal medicine Glucose Intolerance Internal Medicine medicine Animals 030304 developmental biology Secretory Vesicles Sodium channel nutritional and metabolic diseases Secretory Vesicles/physiology medicine.disease Streptozotocin Electrophysiological Phenomena Diabetes Mellitus Type 1 Endocrinology Islet Studies Glucagon-Secreting Cells Hyperglycemia Voltage-Gated Sodium Channels/physiology Hyperglucagonemia |
| Zdroj: | Diabetes, Vol. 62, No 2 (2013) pp. 519-30 Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db11-0786 |
| Popis: | Early-stage type 1 diabetes (T1D) exhibits hyperglucagonemia by undefined cellular mechanisms. Here we characterized α-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 α cells were used to identify α cells within pancreas slices. Mice treated with low-dose STZ exhibited hyperglucagonemia, hyperglycemia, and glucose intolerance, with 71% reduction of β-cell mass. Although α-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 α-cell electrophysiology. α 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 α 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 α cells. |
| Databáze: | OpenAIRE |
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