Cellular processes underlying ontogenesis and regression of streptozotocin (STZ)-induced diabetes in newborn rats were investigated at the most severe stage of diabetes at day 3 and after recovery of normoglycemia at day 8 by immunocytochemistry and quantitative analysis. A previously unknown endocrine cell type subpopulation (PEPS) was identified. It was characterized by granule polymorphism, coexpression of insulin and glucagon immunoreactivity, and a proliferative capacity transiently higher than in B cells. In STZ-treated rats at day 3, B cell mass decreased 14-fold, whereas PEPS cells were unaffected. The islet mass was restored to 55.7% by day 8, with a concomitant appearance of numerous small islets contiguous to small ducts. B cell mass increased by 6.9-fold compared with 1.8-fold in control rats, although proliferative capacities remained similar. Proliferation dropped considerably by day 8, preventing complete B cell mass recovery in STZ-treated rats. STZ-induced neonatal diabetes thus stimulates neogenesis of islets close to ducts and proliferation of PEPS cells. Those partially differentiated islet cells appear to be on the differentiation pathway of stem cells to fully differentiated B cells.
We have determined the cellular distribution of different alpha subtypes of G proteins and adenylyl cyclase (AC) isoforms in endocrine, exocrine, and established pancreatic cell lines. VIP, PACAP, and tGLP-1 receptor proteins are expressed to varying extents in A and B cells, whereas the expression of G alpha subunits is cell specific. Thus, G(olf) alpha is detected in normal rodent B cells and immortalized pancreatic B cell lines, whereas Gs alpha is more ubiquitously expressed. The cellular density of AC isoforms labeling (I, II, III, IV, V/VI) is also islet cell-specific and their distribution is age- and species-dependent. The identification of numerous signaling molecule subtypes, together with the discovery of their specific subcellular distribution, will help the functional characterization of their intraregulatory pathways, leading to the extrusion of insulin or glucagon secretory granules, and those leading to differentiation and apoptosis of islet cells.
SUMMARY1. Hydrolase-related transport was re-investigated in hamster small intestine by the tissue accumulation method.2. The Na+-dependent, phlorizin-sensitive monosaccharide transport system saturates with 30 mM-D-glucose. According to the hydrolase-related transport hypothesis, additional glucose units will be taken up if they are given in the form of a disaccharide susceptible to hydrolysis. But in experiments with [14C]sucrose we found no evidence for any such surplus glucose uptake.3. The uptake of '4C label from sucrose was abolished by using Tris, a strong inhibitor of sucrase, by adding competitive inhibitors of the D-glucose transport system (D-glucose, ,-methyl-D-glucopyranoside or phlorizin), and by substituting Li+ for the Na+ in the incubation medium.4. Glucose and fructose derived from sucrose did not enter the tissues in equimolar amounts: the glucose moiety was taken up much faster.5. We conclude that in hamster intestine there is no evidence for the existence of hydrolase-related transport with sucrose as the monosaccharide donor. The enzymatic hydrolysis of sucrose and the transport of its products, glucose and fructose, are two distinct events, acting sequentially.
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