Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female rats.

OBJECTIVE: To explore the effects of transient correction of enhanced corticoadrenal activity in monosodium L-glutamate (MSG)-damaged female rats on peripheral insulin sensitivity and in vitro retroperitoneal (RP) adipocyte function. DESIGNS: A dose of 4 mg/g body weight (BW) of MSG or vehicle (CTR) was i.p. injected, once every 2 days, between days 2 and 10 of age, in female rats. Intact and 21 day-operated (sham or adrenal enucleation (AE)) rats from both (CTR and MSG) groups were used for experimentation on day 120 of age. Circulating levels of several hormones, in basal and after i.v. high-glucose load conditions, and RP adiposity morphology and function were then evaluated. RESULTS: MSG rats developed increased adrenocortical function, hyperadiposity, hyperleptinemia, hyperinsulinemia and decreased peripheral insulin sensitivity. These characteristics were fully reversed after transient correction of corticoadrenal hyperactivity induced by AE. In addition, in vitro experimentation with isolated RP adipocytes indicated that cells from intact MSG animals displayed decreased sensitivity to insulin and dexamethasone stimulation of leptin secretion. Interestingly, adipocyte dysfunction in MSG rats was fully abrogated after AE-induced transient correction of insulinemia, leptinemia and adrenocortical activity. Importantly, the reversion of these metabolic abnormalities, induced by AE for 21 days, in MSG animals did occur, despite no significant changes in BW values. CONCLUSION: Our results support that the changes in adipocyte characteristics and peripheral insulin resistance, developed in this pseudo-obese female rat model, are mainly due to increased glucocorticoid production. Importantly, appropriate correction of the enhanced adrenocortical activity fully reversed these abnormal functions.

Quantitative ultrastructural changes induced by sucrose administration in the pancreatic B cells of normal hamsters.

We have previously reported that young male Syrian hamsters receiving a sucrose-rich diet presented increased B-cell replication rate and size. The aim of the present study was to analyze, under the same experimental conditions, the ultrastructural changes in B cells. For this purpose, young male Syrian hamsters were fed with a commercial diet and 10% sucrose in their drinking water (S group) while the control group (C) received the same diet and tap water, for 5 weeks. Samples of the pancreas removed after that period were processed for the immunohistochemical identification of B cells as well as for measuring several ultrastructural parameters. S hamsters showed higher serum insulin levels, while similar serum glucose values were obtained in animals from both groups. The B cells from S group exhibited lesser number of dense secretory granules at expenses of an increase of the pale ones, increased number of both exocytosis profiles and fusion-granule images, as well as enlargement of the intercellular space and mitochondrial area. Marked expansions of this space, limited by junctional complexes, were observed between adjacent B cells. These results would indicate that sucrose administration to normal hamsters not only increases the pancreatic B-cell mass but also induces measurable subcellular changes in the individual B-cell characteristic of an enhanced secretory activity. The present model would represent a useful tool for testing strategies in preventing the damage or promoting the recovery of the pancreatic B cells.

Quantitative ultrastructural changes induced by sucrose administration in the pancreatic B cells of normal hamsters.

We have previously reported that young male Syrian hamsters receiving a sucrose-rich diet presented increased B-cell replication rate and size. The aim of the present study was to analyze, under the same experimental conditions, the ultrastructural changes in B cells. For this purpose, young male Syrian hamsters were fed with a commercial diet and 10

sucrose in their drinking water (S group) while the control group (C) received the same diet and tap water, for 5 weeks. Samples of the pancreas removed after that period were processed for the immunohistochemical identification of B cells as well as for measuring several ultrastructural parameters. S hamsters showed higher serum insulin levels, while similar serum glucose values were obtained in animals from both groups. The B cells from S group exhibited lesser number of dense secretory granules at expenses of an increase of the pale ones, increased number of both exocytosis profiles and fusion-granule images, as well as enlargement of the intercellular space and mitochondrial area. Marked expansions of this space, limited by junctional complexes, were observed between adjacent B cells. These results would indicate that sucrose administration to normal hamsters not only increases the pancreatic B-cell mass but also induces measurable subcellular changes in the individual B-cell characteristic of an enhanced secretory activity. The present model would represent a useful tool for testing strategies in preventing the damage or promoting the recovery of the pancreatic B cells.

[Structure and ultrastructure of the endocrine pancreas in diabetic transgenic mice]. / Estructura y ultraestructura del páncreas endocrino de ratones transgénicos diabéticos.

The aim of the present study was to confirm the structural changes and to establish the ultrastructural alterations that occur in the endocrine pancreas of mice with an induced insulin-dependent diabetes mellitus (IDDM) syndrome. For that purpose, we used transgenic mice (OVE 27) that overexpress a calmodulin gene in the beta cells of the endocrine pancreas. In these animals, the excess of calmodulin decreases the cytosolic calcium levels in beta cells, leading to morphological and functional alterations that produce a severe IDDM. Sections of pancreas (tail) from 4 male 5-week-old diabetic mice (glycemia: 376 +/- 2 mg/dl) and from 4 normal age-matched males (glycemia: 113 +/- 13 mg/dl) were processed. Light microscopic immunohistochemical observations confirmed a decrease in the number and size of pancreatic islets in transgenic mice, together with a disruption in their architecture, without an associated inflammatory response. The ultrastructural studies revealed diverse degrees of injury in the beta cells, such as the presence of membrane interdigitations and alterations in their organelles and secretory granules. These findings are in agreement with the quantitative and functional impairment of beta cells, coexisting with a normal appearance of non-beta cell populations within the pancreatic islets. Our results demonstrate the existence of ultrastructural changes in the pancreatic beta cells of the experimental model studied. Such changes, together with the immunohistochemical alterations previously described, contribute to explain the appearance of a diabetic syndrome in these animals.