In vivo measurement and biological characterisation of the diabetes-associated mutant insulin p.R46Q (GlnB22-insulin).

ABSTRACT:

Aims/hypothesis

Heterozygous mutations in the insulin gene that affect proinsulin biosynthesis and folding are associated with a spectrum of diabetes phenotypes, from permanent neonatal diabetes to MODY. In vivo studies of these mutations may lead to a better understanding of insulin mutation-associated diabetes and point to the best treatment strategy. We studied an 18-year-old woman with MODY heterozygous for the insulin mutation p.R46Q (GlnB22-insulin), measuring the secretion of mutant and wild-type insulin by LC-MS. The clinical study was combined with in vitro studies of the synthesis and secretion of p.R46Q-insulin in rat INS-1 insulinoma cells.

Methods

We performed a standard 75 g OGTT in the 18-year-old woman and measured plasma glucose and serum insulin (wild-type

SUBMITTER: Stoy J 

PROVIDER: S-EPMC8785399 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature