Potent humanin analog increases glucose-stimulated insulin secretion through enhanced metabolism in the cell

Regina Kuliawat, Laura Klein, Zhenwei Gong, Marianna Nicoletta-Gentile, Anjana Nemkal, Lingguang Cui, Claire Bastie, Kai Su, Derek Huffman, Manju Surana, Nir Barzilai, Norman Fleischer, Radhika Muzumdar

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4890-4898
Number of pages9
JournalFASEB Journal
Volume27
Issue number12
DOIs
StatePublished - Dec 1 2013

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Keywords

  • Diabetes
  • Hyperglycemic clamps
  • Pancreatic islets

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

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. (2013). Potent humanin analog increases glucose-stimulated insulin secretion through enhanced metabolism in the cell. FASEB Journal, 27(12), 4890-4898. https://doi.org/10.1096/fj.13-231092