题名：Potent humanin analog increases glucose-stimulated insulin secretion through enhanced metabolism in the beta cell.
作者：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;
来源：FASEB J. 2013 Dec;27(12):4890-8. doi: 10.1096/fj.13-231092. Epub 2013 Aug 30. [ IF= 0.00 ] ]
摘要：Humanin (HN) is a 24-aa polypeptide that offers protection from Alzheimer's
disease and myocardial infarction, increases insulin sensitivity, improves
survival of beta 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 beta cell line (betaTC3) 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 betaTC3 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 beta 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 beta cell.