Objective-To investigate whether low vitamin E status is a risk factor for incident non-insulin dependent diabetes mellitus.Design-Population based follow up study with diabetes assessed at baseline and at four years.Setting-Eastern Finland. Subjects-Random sample of 944 men aged 42-60 who had no diabetes at the baseline examination.Intervention-Oral glucose tolerance test at four year follow up.Main outcome measures-A man was defined diabetic if he had either (a) a fasting blood glucose concentration ¢ 6-7 mmol/l, or (b) a blood glucose concentration ¢ 10*0 mmol/l two hours after a glucose load, or (c) a clinical diagnosis of diabetes with either dietary, oral, or insulin treatment.Results-45 men developed diabetes during the follow up period. In a multivariate logistic regression model including the strongest predictors ofdiabetes, a low lipid standardised plasma vitamin E (below median) concentration was associated with a 3 9-fold (95'!. confidence interval 18-fold to 8.6-fold) risk of incident diabetes. A decrement of 1 ,umol/l of uncategorised unstandardised vitamin E concentration was associated with an increment of 22% in the risk of diabetes when allowing for the strongest other risk factors as well as serum low density lipoprotein cholesterol and triglyceride concentrations.Conclusions-There was a strong independent association between low vitamin E status before follow up and an excess risk ofdiabetes at four years. This supports the theory that free radical stress has a role in the causation of non-insulin dependent diabetes mellitus.

Osteopontin, a major noncollagenous bone protein, is an in vitro and in vivo substrate of tissue transglutaminase, which catalyzes formation of cross-linked protein aggregates. The roles of the enzyme and the polymeric osteopontin are presently not fully understood. In this study we provide evidence that transglutaminase treatment significantly increases the binding of osteopontin to collagen. This was tested with an enzyme-linked immunosorbent assay. The results also show that this increased interaction is clearly calcium-dependent and specific to osteopontin. In dot blot overlay assay 1 g of collagen type I was able to bind 420 ng of in vitro prepared and purified polymeric osteopontin and only 83 ng of monomeric osteopontin, indicating that the transglutaminase treatment introduces a 5-fold amount of osteopontin onto collagen. Assays using a reversed situation showed that the collagen binding of the polymeric form of osteopontin appears to be dependent on its conformation in solution. Circular dichroism analysis of monomeric and polymeric osteopontin indicated that transglutaminase treatment induces a conformational change in osteopontin, probably exposing motives relevant to its interactions with other extracellular molecules. This altered collagen binding property of osteopontin may have relevance to its biological functions in tissue repair, bone remodeling, and collagen fibrillogenesis.Tissue transglutaminase (TG) 1 (EC 2.3.2.13) is a widely distributed intra-and extracellular calcium-dependent enzyme, which catalyzes the formation of high molecular mass complexes of its substrate proteins by creating isopeptide crosslinks from glutamine and lysine residues and releasing ammonia (1, 2). TG is suggested to be involved in matrix maturation and stabilize the tissue with cross-links that are resistant to normal proteolysis (1, 2). TG is closely related to wound healing which suggests a role for it in tissue remodeling and repair (3,4). Immunohistochemical data have also demonstrated the presence of TG in mineralizing cartilage and bone (5, 6) and the enzyme is thought to participate in matrix cross-linking before the tissue undergoes calcification (5, 6). The number of proteins serving as glutaminyl substrates for TG is restricted indicating the physiological importance of its functions (1). The roles of TG and the actions of its enzymatic products, meaning high molecular weight proteins, are still unclear.Osteopontin (OPN), a prominent and potentially multifunctional acidic phosphoglycoprotein (7,8), is a substrate of TG (9 -11). OPN is a major product of bone forming cells, osteoblasts, but is not specific to bone. It is also synthesized in other types of tissues and found in, e.g. inner ear, brain, kidney (7), and atherosclerotic plaques (13,14), and it is also secreted into milk (12) and urine (15). Its production is also related to immunity, infection, and cancer (8). Osteoblasts express OPN at an early developmental stage of bone formation (16,17). In bone, OPN is deposited into unmineralized matrix pri...

Intravenous administration of D-fructose to rats rapidly depletes liver adenosine triphosphate and inorganic phosphate; marked elevations of uric acid and allantoin in plasma follow. Concomitantly the incorporation of DL-leucine-1-(14)C into liver protein is almost completely inhibited.

No abstract