An extract from oats known as oat gum (OG) is composed mainly of the polysaccharide (1 + 3) (1 + 4)-/?--D-glucan, which is highly viscous in aqueous solution. Viscous polysaccharides are known to attenuate postprandial plasma glucose and insulin responses. The purposes of this study were to determine the doseresponse to OG and establish quantitatively the effect of viscosity on plasma glucose and insulin levels of healthy humans consuming 50 g glucose. Increasing the dose of OG successively reduced the plasma glucose and insulin responses relative to a control without gum. Reduction of the viscosity of OG by acid hydrolysis reduced or eliminated the capacity to decrease postprandial glucose and insulin levels. The ability of OG to modify glycaemic response was unchanged following agglomeration in the presence of maltodextrin. Agglomerated gum dispersed smoothly in a drink without formation of lumps, and development of maximum viscosity was delayed. These properties improve palatability. There was a highly significant linear relationship between loglviscosity] of the mixtures consumed and the glucose and insulin responses. The relationship shows that 7S96 YO of the changes in plasma glucose and insulin are attributable to viscosity, and that changes occur at relatively low doses and viscosities.

Objective Spinal muscular atrophy (SMA) is the number 1 genetic killer of young children. It is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Although SMA is primarily a motor neuron disease, metabolism abnormalities such as metabolic acidosis, abnormal fatty acid metabolism, hyperlipidemia, and hyperglycemia have been reported in SMA patients. We thus initiated an in-depth analysis of glucose metabolism in SMA. Methods Glucose metabolism and pancreas development were investigated in the Smn2B/− intermediate SMA mouse model and type I SMA patients. Results Here, we demonstrate in an SMA mouse model a dramatic cell fate imbalance within pancreatic islets, with a predominance of glucagon-producing α cells at the expense of insulin-producing β cells. These SMA mice display fasting hyperglycemia, hyperglucagonemia, and glucose resistance. We demonstrate similar abnormalities in pancreatic islets from deceased children with the severe infantile form of SMA in association with supportive evidence of glucose intolerance in at least a subset of such children. Interpretation Our results indicate that defects in glucose metabolism may play an important contributory role in SMA pathogenesis.

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The Lkb1 tumor suppressor exerts its biological effects through phosphorylation and consequent activation of the AMP kinase (AMPK) family. Extensive genetic and biochemical evidence supports a role for Lkb1 in cell cycle arrest, establishment of cell polarity, and cellular energy metabolism. However, the role of Lkb1 and the AMPK family in beta cell function in vivo has not been established. We generated conditional knockout mice with a deletion of the Lkb1 gene in the beta cell compartment of pancreatic islets; these mice display improved glucose tolerance and protection against diet-induced hyperglycemia. Lkb1(-/-) beta cells are hypertrophic because of elevated mTOR activity; they also proliferate more and secrete more insulin in response to glucose. These data indicate that inhibiting Lkb1 activity in beta cells may facilitate beta cell expansion and glucose tolerance in vivo.

a b s t r a c tProprotein convertase subtilisin/kexin type 9 (PCSK9), a liver-secreted plasma enzyme, restricts hepatic uptake of low-density lipoprotein (LDL) cholesterol by promoting the degradation of LDL receptors (LDLR). PCSK9 and LDLR are also expressed in insulin-producing pancreatic islet b cells, possibly affecting the function of these cells. Here we show that, compared to control mice, PCSK9-null male mice over 4 months of age carried more LDLR and less insulin in their pancreas; they were hypoinsulinemic, hyperglycemic and glucose-intolerant; their islets exhibited signs of malformation, apoptosis and inflammation. Collectively, these observations suggest that PCSK9 may be necessary for the normal function of pancreatic islets.

The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, BRONNER-BENDER Stiftung/Gernsbach, University Children's Hospital Zurich.

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We evaluated the relation between early infant diet and insulin-dependent diabetes risk with a meta-analysis of 17 case-control studies. A summary of all studies indicated a moderate effect for exposure to breast-milk substitutes [odds ratio (OR) = 1.38; 95% confidence interval (CI) = 1.18-1.61] and cow's milk-based substitutes (OR = 1.61; 95% CI = 1.31-1.98) before 3 months of age. Fourteen studies relied on retrospectively collected infant diet data based on long-term maternal recall, which may be biased or inaccurate; three studies used existing infant diet records to assess exposure, thus lessening the possibility of recall bias or inaccurate data. The studies using existing records demonstrated little association compared with the studies relying on long-term recall. Studies in which the controls had a participation rate that was more than 20% lower than that of the cases showed a stronger diabetogenic effect of never being breast-fed (OR = 1.58) than studies whose cases and controls had similar participation rates (OR = 1.06). Thus, differences in the participation rates of cases and controls may have biased the results of these studies. This meta-analysis indicates that the weak association between infant diet and risk of diabetes mellitus may have methodologic explanations.