Subclinical Diabetes

ABSTRACT Type 2 diabetes mellitus (T2DM) is increasing in prevalence worldwide, and those non-diagnosed or misdiagnosed comprise a significant group compared to those diagnosed. Accumulated scientific evidence indicate that the current diagnostic markers (fasting glycemia, 2h glycemia after an oral glucose load and HbA1c) are indeed late diagnostic criteria when considering the incidence of diabetes-related complications and comorbidities, which are also at high risk in some groups among normoglycemic individuals. Additionally, the earlier identification of future risk of diabetes is desirable since it would allow better adherence to preventive actions such as lifestyle intervention, ultimately avoiding complications and minimizing the economic impact/burden on health care expenses. Insulin resistance and hyperhormonemia (insulin, amylin, glucagon) are non-disputable hallmarks of T2DM, which already takes place among these normoglycemic, otherwise health subjects, characterizing a state of subclinical diabetes. Insulin resistance and hyperinsulinemia can be computed from fasting plasma insulin as an independent variable in normoglycemia. An overview of the current diagnostic criteria, disease onset, complications, comorbidities and perspectives on lifestyle interventions are presented. A proposal for early detection of subclinical diabetes from routine evaluation of fasting plasma insulin, which is affordable and robust and thus applicable for the general population, is further suggested

Amylin induces hypoglycemia in mice

Amylin is a 37-aminoacid pancreatic protein that exerts control over several metabolic events such as glycemia and lacticemia. Amylin has long been shown to induce increases in arterial plasma glucose. We decided to investigate whether amylin plays additional roles in the glucose metabolism. We evaluated glucose homeostasis using whole blood from the tail tip of fasting, conscious, unrestrained normal and streptozotocyn-induced diabetic mice following subcutaneous administration of mouse amylin. Subcutaneous injection of 1 μg mouse amylin caused a transient decrease in whole blood glucose in both normal and diabetic mice in the absence of insulin. The blood glucose levels were lowest approximately 2 hours after amylin administration, after that they gradually recovered to the levels of the control group. The hypoglycemic effect followed a dose-dependent response ranging from 0.1 to 50 µg / mouse. These results reveal the ability for amylin in the direct control of glycemia at low doses in the absence of insulin

The Amino-Terminal PrP Domain Is Crucial to Modulate Prion Misfolding and Aggregation

The main hypothesis for prion diseases is that the cellular protein (PrP(C)) can be altered into a misfolded, β-sheet-rich isoform (PrP(Sc)), which undergoes aggregation and triggers the onset of transmissible spongiform encephalopathies. Here, we investigate the effects of amino-terminal deletion mutations, rPrP(Δ51–90) and rPrP(Δ32–121), on the stability and the packing properties of recombinant murine PrP. The region lacking in rPrP(Δ51–90) is involved physiologically in copper binding and the other construct lacks more amino-terminal residues (from 32 to 121). The pressure stability is dramatically reduced with decreasing N-domain length and the process is not reversible for rPrP(Δ51–90) and rPrP(Δ32–121), whereas it is completely reversible for the wild-type form. Decompression to atmospheric pressure triggers immediate aggregation for the mutants in contrast to a slow aggregation process for the wild-type, as observed by Fourier-transform infrared spectroscopy. The temperature-induced transition leads to aggregation of all rPrPs, but the unfolding temperature is lower for the rPrP amino-terminal deletion mutants. The higher susceptibility to pressure of the amino-terminal deletion mutants can be explained by a change in hydration and cavity distribution. Taken together, our results show that the amino-terminal region has a pivotal role on the development of prion misfolding and aggregation