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Articles by L. W. Harries
Total Records ( 2 ) for L. W. Harries
  R. Singh , A. T. Hattersley and L. W. Harries
 

Aims  Mitochondrial depletion in pancreatic beta cells is known to reduce glucose stimulated insulin secretion. We aimed to determine whether the offspring of patients with early onset Type 2 diabetes had reduced peripheral blood mitochondrial content relative to control subjects and whether this could lead to a predisposition to type 2 diabetes in later life.

Methods  We measured the levels of mitochondria relative to a single copy genomic target by real time polymerase chain reaction in a series of peripheral blood samples taken from the offspring of Caucasian patients with Type 2 diabetes and matched controls. Measures of insulin sensitivity and beta cell function were also taken.

Results  In contrast with previous studies, mitochondrial DNA content was not decreased in the offspring of patients with Type 2 diabetes relative to matched controls in our cohort. Conversely, we noted a small proliferation in mitochondrial numbers in our case subjects. In agreement with these findings, no correlations with either insulin sensitivity or beta cell function were noted.

Conclusions  Our results indicate that reduced mitochondrial DNA content in peripheral blood is not a risk factor for the development of Type 2 diabetes in the offspring of patients with early onset Type 2 diabetes.

  A. Wirsing , K. A. Johnstone , L. W. Harries , S. Ellard , G. U. Ryffel , J. Stanik , D. Gasperikova , I. Klimes and R. Murphy
  Aims  Mutations in HNF4A cause a form of monogenic β-cell diabetes. We aimed to identify mutations in the pancreas-specific P2 promoter of HNF4A in families with suspected HNF4A diabetes and to show that they impaired the function of the promoter in vitro.
Methods 
We screened families with a clinical suspicion of HNF4A monogenic β-cell diabetes for mutations in the HNF4A P2 promoter. We investigated the function of the previously reported HNF4A P2 promoter mutation −192C>G linked to late-onset diabetes in several families, along with two new segregating mutations, in vitro using a modified luciferase reporter assay system with enhanced sensitivity.
Results 
We identified two novel HNF4A P2 promoter mutations that co-segregate with diabetes in two families, −136A>G and −169C>T. Both families displayed phenotypes typical of HNF4A monogenic β-cell diabetes, including at least two affected generations, good response to sulphonylurea treatment and increased birthweight and/or neonatal hypoglycaemia. We show that both of these novel mutations and −192C>G impair the function of the promoter in transient transfection assays.
Conclusions 
Two novel mutations identified here and the previously identified late-onset diabetes mutation, −192C>G, impair the function of the HNF4A P2 promoter in vitro.
 
 
 
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