PURPOSE To assess the associations among baseline levels of fasting insulin and proinsulin, proinsulin:insulin ratio, and the development of type 2 diabetes mellitus in apparently healthy middle-aged women. METHODS In a nested case-control study involving a nationwide cohort of 27,628 participants from the Women's Health Study, 126 women with diabetes diagnosed during a 4-year follow-up perio...

Beyond Blood Sugar: Early Diabetes Detection in Cats The type of diabetes cats develop is believed to be similar to type 2 diabetes in humans (i.e., islet amyloid develops but not antibodies against beta cells). However, most cats require insulin therapy by the time they are presented for diabetes, implying that they are diagnosed belatedly in the disease process, after significant structural b...

An intermediate in the biosynthesis of insulin has been isolated from anglerfish islets and shown to have the structure of insulin with the additional amino acid residues GlyThr-Lys attached to the NH2 terminus of the A chain. This intermediate can be produced in vitro by a rapid tryptic enzymic cleavage of anglerfish proinsulin; more extensive trypsin treatment converts this intermediate to in...

The exact nature of the -cell defect in type 2 diabetic patients is still unclear. -Cell mass reduction has been reported but remains controversial. A preliminary study of a large series of patients has demonstrated that in most, the -cell defect is not related to a decreased -cell mass. Amyloid deposits are observed in the islets of some type 2 diabetic patients but also in normoglycemic subje...

Monensin, a specific sodium ionophore~ has been shown to reduce glucose-induced proinsulin biosynthesis by 30% and to completely inhibit ~he intracellular conversion of proinsul in to insulin. Autoradiography of monensint r e a t e d cells d e m o n s t r a t e d the p resence of large quantities of newly synthesized proteins in amorphous vesicles close to the Golgi complex of B ceils. The r e ...

The biological activities of several derivatives of human proinsulin (HPI) containing peptide bond cleavages or peptide deletions in the connecting peptide region were examined in vivo in rats and in several in vitro systems. The two derivatives which were tested in vivo, split (32-33)HPI and des-(64,65)HPI, both demonstrated greater potency in lowering blood glucose than did intact HPI. The re...

Insulin secretion from pancreatic beta cells is dependent on maturation and acidification of the secretory granule, processes necessary for prohormone convertase cleavage of proinsulin. Previous studies in isolated beta cells revealed that acidification may be dependent on the granule membrane chloride channel ClC-3, in a step permissive for a regulated secretory response. In this study, immuno...

The renal extraction and excretion of bovine proinsulin, insulin, and C-peptide and the contribution of the kidney to their total metabolic clearance rate (MCR) were studied in the rat. Metabolic clearance rates were measured by the constant infusion technique and plasma and urine concentrations of each polypeptide were determined by radioimmunoassay. The MCR of insulin (16.4+/-0.4 ml/min) was ...

Islets of Langerhans isolated from rat pancreas were incubated at 37 degrees C(95% O(2)/5% CO(2)) in buffered medium containing 1.0 mg/ml glucose and leucine (3)H for 1 hr (1st hr), washed, and incubated for an additional hr (2nd hr) in low glucose medium (0.5-1.0 mg/ml) containing unlabeled leucine. A portion of the islets was then extracted with acid-ethanol and the remainder were transferred...

We have obtained evidence by autoradiography and immunocytochemistry that mature secretory granules of the pancreatic B-cell gain access to a lysosomal compartment (multigranular or crinophagic bodies) where the secretory granule content is degraded. Whereas the mature secretory granule content shows both insulin and C-peptide (proinsulin) immunoreactivities, in crinophagic bodies only insulin,...