TY - JOUR
T1 - Potent humanin analog increases glucose-stimulated insulin secretion through enhanced metabolism in the cell
AU - Kuliawat, Regina
AU - Klein, Laura
AU - Gong, Zhenwei
AU - Nicoletta-Gentile, Marianna
AU - Nemkal, Anjana
AU - Cui, Lingguang
AU - Bastie, Claire
AU - Su, Kai
AU - Huffman, Derek
AU - Surana, Manju
AU - Barzilai, Nir
AU - Fleischer, Norman
AU - Muzumdar, Radhika
PY - 2013/12
Y1 - 2013/12
N2 - Humanin (HN) is a 24-aa polypeptide that offers protection from Alzheimer's disease and myocardial infarction, increases insulin sensitivity, improves survival of cells, and delays onset of diabetes. Here we examined the acute effects of HN on insulin secretion and potential mechanisms through which they are mediated. Effects of a potent HN analog, HNGF6A, on glucose-stimulated insulin secretion (GSIS) were assessed in vivo and in isolated pancreatic islets and cultured murine cell line (TC3) in vitro. Sprague- Dawley rats (3 mo old) that received HNGF6A required a significantly higher glucose infusion rate and demonstrated higher insulin levels during hyperglycemic clamps compared to saline controls. In vitro, compared to scrambled peptide controls, HNGF6A increased GSIS in isolated islets from both normal and diabetic mice as well as in TC3 cells. Effects of HNGF6A on GSIS were dose dependent, K-ATP channel independent, and associated with enhanced glucose metabolism. These findings demonstrate that HNGF6A increases GSIS in whole animals, from isolated islets and from cells in culture, which suggests a direct effect on the cell. The glucose-dependent effects on insulin secretion along with the established effects on insulin action suggest potential for HN and its analogs in the treatment of diabetes.-Kuliawat, R., Klein, L., Gong, Z., Nicoletta-Gentile, M., Nemkal, A. Cui, L., Bastie, C., Su, K., Huffman, D., Surana, M., Barzilai, N., Fleischer, N., Muzumdar, R. Potent humanin analog increases glucose-stimulated insulin secretion through enhanced metabolism in the cell.
AB - Humanin (HN) is a 24-aa polypeptide that offers protection from Alzheimer's disease and myocardial infarction, increases insulin sensitivity, improves survival of cells, and delays onset of diabetes. Here we examined the acute effects of HN on insulin secretion and potential mechanisms through which they are mediated. Effects of a potent HN analog, HNGF6A, on glucose-stimulated insulin secretion (GSIS) were assessed in vivo and in isolated pancreatic islets and cultured murine cell line (TC3) in vitro. Sprague- Dawley rats (3 mo old) that received HNGF6A required a significantly higher glucose infusion rate and demonstrated higher insulin levels during hyperglycemic clamps compared to saline controls. In vitro, compared to scrambled peptide controls, HNGF6A increased GSIS in isolated islets from both normal and diabetic mice as well as in TC3 cells. Effects of HNGF6A on GSIS were dose dependent, K-ATP channel independent, and associated with enhanced glucose metabolism. These findings demonstrate that HNGF6A increases GSIS in whole animals, from isolated islets and from cells in culture, which suggests a direct effect on the cell. The glucose-dependent effects on insulin secretion along with the established effects on insulin action suggest potential for HN and its analogs in the treatment of diabetes.-Kuliawat, R., Klein, L., Gong, Z., Nicoletta-Gentile, M., Nemkal, A. Cui, L., Bastie, C., Su, K., Huffman, D., Surana, M., Barzilai, N., Fleischer, N., Muzumdar, R. Potent humanin analog increases glucose-stimulated insulin secretion through enhanced metabolism in the cell.
KW - Diabetes
KW - Hyperglycemic clamps
KW - Pancreatic islets
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UR - http://www.scopus.com/inward/citedby.url?scp=84890544217&partnerID=8YFLogxK
U2 - 10.1096/fj.13-231092
DO - 10.1096/fj.13-231092
M3 - Article
C2 - 23995290
AN - SCOPUS:84890544217
SN - 0892-6638
VL - 27
SP - 4890
EP - 4898
JO - FASEB Journal
JF - FASEB Journal
IS - 12
ER -
