Pancreatic islets from cyclin-dependent kinase 4/R24C (Cdk4) knockin mice have significantly increased beta cell mass and are physiologically functional, indicating that Cdk4 is a potential target for pancreatic beta cell mass regeneration in Type 1 diabetes.

Aims/hypothesis: Cyclin-dependent kinase 4 (Cdk4) is crucial for beta cell development. A mutation in the gene encoding for Cdk4, Cdk4R24C, causes this kinase to be insensitive to INK4 cell cycle inhibitors and induces beta cell hyperplasia in Cdk4R24C knockin mice. We aimed to determine whether this Cdk4R24C mutation also affects proper islet function, and whether it promotes proliferation in human islets lentivirally transduced with Cdk4R24C cDNA.

Transcript expression of two Iglambda rearrangements and RAG-1/RAG-2 in a mature human B cell producing IgMlambda islet cell autoantibody.

A human B cell clone, EBV-MB91, producing IgMlambda islet cell autoantibody (ICA), obtained by Epstein-Barr virus (EBV) transformation of peripheral CD5- surface Ig+ B cells from a Type 1 diabetic child, and an EBV-MB91-derived hetrohybridoma, HY-MB91, were analyzed for rearranged Ig genes. Both EBV-MB91 and HY-MB91 contained and expressed a unique IgH chain rearrangement (unmutated VH5-51-D6-19-JH5) but contained and expressed two Iglambda chain rearrangements: (i) Vlambda1-4-Jlambda3-Clambda3, which encoded the Iglambda chains (pI, 8.0) of IgMlambda-ICA, showing few mutations but consistent with Ag-driven selection according to the multinomial probability model; and (ii) Vlambda4-1-Jlambda3-Clambda3, with more mutations but inconsistent with antigen-driven selection and involving stop codons that precluded Iglambda synthesis.

Identification and functional analysis of mutations in FAD-binding domain of mitochondrial glycerophosphate dehydrogenase in caucasian patients with type 2 diabetes mellitus.

Ca2+-responsive mitochondrial FAD-linked glycerophosphate dehydrogenase (mGPDH) is a key component of the pancreatic beta-cell glucose-sensing device. The purpose of this study was to examine the association of mutations in the cDNA coding for the FAD-binding domain of mGPDH and to explore the functional consequences of these mutations in vitro. To investigate this association in type 2 diabetes mellitus, we studied a cohort of 168 patients with type 2 diabetes and 179 glucose-tolerant control subjects of Spanish Caucasian origin by single-stranded conformational polymorphism analysis.