Association of a polymorphism in the betacellulin gene with type 1 diabetes mellitus in two populations

  title={Association of a polymorphism in the betacellulin gene with type 1 diabetes mellitus in two populations},
  author={Kristi D Silver and Victoria L. Magnuson and Magdalena I. Tolea and Jian Wang and William A. Hagopian and Braxton D. Mitchell},
  journal={Journal of Molecular Medicine},
Betacellulin, a member of the epidermal growth factor family, is expressed in fetal and adult pancreas. In vitro and in vivo studies suggest a role for betacellulin in islet neogenesis and regeneration. Therefore, a mutation in the betacellulin gene might lead to fewer beta cells. With reduced beta cell reserve, beta cells may not be able to compensate for an autoimmune attack, and in turn, susceptibility to type 1 diabetes mellitus (T1DM) would increase. Previous mutational analysis identified… 
Analysis of coding variants in the betacellulin gene in type 2 diabetes and insulin secretion in African American subjects
It is unable to confirm a role for nonsynonymous variants of betacellulin in the propensity to type 2 diabetes or to impaired insulin secretion, but an effect on lipids was observed for all 3 variants, and variant L124M was associated with obesity measures.
Knowledge Gaps in Rodent Pancreas Biology: Taking Human Pluripotent Stem Cell-Derived Pancreatic Beta Cells into Our Own Hands
The efforts here unravel several novel signaling pathways that can be further studied to shed light on unexplored aspects of rodent pancreas biology and to aid in the translation of stem cell biology in the context of diabetes treatments.


The exon 1 Cys7Gly polymorphism within the betacellulin gene is associated with type 2 diabetes in African Americans.
Seven polymorphisms in segments encompassing the 5' untranslated region, including the Gly7 variant, were identified and determined that betacellulin was expressed in 9- to 24-week-old human fetal pancreas.
Association of polymorphism in the NeuroD/BETA2 gene with type 1 diabetes in the Japanese.
Because the variant of the NeuroD/BETA2 gene (Ala45Thr) is associated with type 1 but not type 2 diabetes, it may be implicated in the loss of pancreatic beta-cells in type 1 diabetes.
Association of childhood type 1 diabetes mellitus with a variant of PAX4: possible link to beta cell regenerative capacity
A link between beta cell regenerative capacity and susceptibility to type 1 diabetes is identified, which could explain the fact that not all of the individuals who develop autoimmunity against beta cells actually contract the disease.
Betacellulin-δ4, a Novel Differentiation Factor for Pancreatic β-Cells, Ameliorates Glucose Intolerance in Streptozotocin-Treated Rats
BTC-4 is a secreted protein that stimulates differentiation of -cells in vitro and in vivo in an apparent ErbB1- and Erb B4-independent manner and presumably involves an, as yet, unidentified unique receptor.
Betacellulin-delta4, a novel differentiation factor for pancreatic beta-cells, ameliorates glucose intolerance in streptozotocin-treated rats.
BTC-delta4 is a secreted protein that stimulates differentiation of beta-cells in vitro and in vivo in an apparent ErbB1- and Erb B4-independent manner.
A role for activin A and betacellulin in human fetal pancreatic cell differentiation and growth.
Data suggest that Act.A induces endocrine differentiation, whereasBTC has a mitogenic effect on human undifferentiated pancreatic epithelial cells, whereas BTC alone caused a 2.6-fold increase in DNA synthesis.
Human betacellulin, a member of the EGF family dominantly expressed in pancreas and small intestine, is fully active in a monomeric form.
Recombinant BTC showed growth promoting activity for mouse fibroblasts and rat aortic smooth muscle cells which was equivalent to EGF On the other hand, BTC was found to exhibit a growth inhibitory effect on the cells overexpressing EGF receptor.
Recombinant human betacellulin promotes the neogenesis of beta-cells and ameliorates glucose intolerance in mice with diabetes induced by selective alloxan perfusion.
Administration of rhBTC improved glucose tolerance in this mouse model by increasing beta-cell volume, primarily through accelerated neogenesis from ductal lining cells.
Common variants in glutamine:fructose-6-phosphate amidotransferase 2 (GFPT2) gene are associated with type 2 diabetes, diabetic nephropathy, and increased GFPT2 mRNA levels.
GFPT2 mRNA levels in transformed lymphocytes from study subjects were significantly increased among African-American subjects compared with Caucasian individuals, regardless of diagnosis, and the associated allele of the 3' UTR SNP was approximately 2-fold overexpressed.
Islet Mass and Function in Diabetes and Transplantation
Difficulty obtaining sufficient amounts of β-cell tissue is expected to remain a barrier to successful islet transplantation for the immediate future and more should be learned about the function and fate of grafted islet cells.