Vesiculin derived from IGF-II drives increased islet cell mass in a mouse model of pre-diabetes. Issue 1 (1st January 2022)

• Record Type: Journal Article
• Authors: Lee, Kate L.; Aitken, Jacqueline F.; Li, Xun; Montgomery, Kirsten; Hsu, Huai-L.; Williams, Geoffrey M.; Brimble, Margaret A.; Cooper, Garth J.S.
• Is Part Of: Islets. Volume 14:Issue 1(2022)
• Page Start: 14
• Page End: 22
• Publication Date: 2022-01-01
• Subjects: IGF-II -- beta-cell -- pancreatic islets -- hormone -- diabetes -- insulin; Islands of Langerhans -- Periodicals; Pancreas -- Periodicals; 616.46
• DOI: 10.1080/19382014.2021.1982326
• Languages: English
• ISSNs: 1938-2022

Abstract

ABSTRACT: Pancreatic islet-cell function and volume are both key determinants of the maintenance of metabolic health. Insulin resistance and islet-cell dysfunction often occur in the earlier stages of type 2 diabetes (T2D) progression. The ability of the islet cells to respond to insulin resistance by increasing hormone output accompanied by increased islet-cell volume is key to maintaining blood glucose control and preventing further disease progression. Eventual β-cell loss is the main driver of full-blown T2D and insulin-dependency. Researchers are targeting T2D with approaches that include those aimed at enhancing the function of the patient's existing β-cell population, or replacing islet β-cells. Another approach is to look for agents that enhance the natural capacity of the β-cell population to expand. Here we aimed to study the effects of a new putative β-cell growth factor on a mouse model of pre-diabetes. We asked whether: 1) 4-week's treatment with vesiculin, a two-chain peptide derived by processing from IGF-II, had any measurable effect on pre-diabetic mice vs vehicle; and 2) whether the effects were the same in non-diabetic littermate controls. Although treatment with vesiculin did not alter blood glucose levels over this time period, there was a doubling of the Proliferating Cell Nuclear Antigen (PCNA) detectable in the islets of treated pre-diabetic but not control mice and this was accompanied by increased insulin- and glucagon-positive stained areas in the pancreatic islets.