Plasma D-glucose Research Articles

Induction and Reversibility of Insulin Resistance in Rats Exposed to ExogenousD-Fructose

Long-term exposure of normal rats to a fructose-enriched diet or drinking water is currently used as an animal model for experimental insulin resistance. The present study deals with a comparison between rats given access to either a fructose-enriched diet or fructose-enriched drinking water. In both situations, a decrease in food intake and body weight gain, and the induction of insulin resistance with intolerance to D-glucose despite increased secretory response to the aldohexose of insulin-producing cells were documented. Moreover, the rats exposed to exogenous D-fructose displayed a lesser sensitivity to overnight fasting than control animals, in terms of the alteration of glucose homeostasis and reduction of the ratio between plasma insulin and D-glucose concentration. It is also shown that the fructose-induced insulin resistance, as assessed in a hyperinsulinemic-euglycemic clamp, represents a phenomenon reversed within 15-30 days after removal of the keto-hexose from the drinking water.

Glucose Intolerance Associated to Insulin Resistance and Increased Insulin Secretion in Rats Depleted in Long-chain ω3 Fatty Acids

An intragastric D-glucose tolerance test was performed, after overnight starvation, in female rats depleted in long-chain polyunsaturated omega3 fatty acids (omega3D rats) and control rats of same age and gender. The plasma D-glucose and insulin concentrations, insulinogenic index, and HOMA for insulin resistance were all higher, after overnight starvation, in omega3D rats than in control animals. Over the 120-minute period following the intragastric administration of D-glucose, the area under the curve for the same four variables was also higher in omega3D rats than in control animals. In addition to visceral obesity, liver steatosis, hypertension, and cardiac hypertrophy, the omega3D rats thus display further features of the metabolic syndrome, namely glucose intolerance and insulin resistance, despite hyperinsulinemia.

Effects of diet supplementation with olive oil and guar upon fructose-induced insulin resistance in normal rats

Exposure of normal rats to fructose-containing drinking water represents a current model of insulin resistance. The major aim of the present study was to assess the possible effect of diet supplementation with either olive oil or guar upon the metabolic consequences of exposure to exogenous fructose. For this purpose, the changes in body weight, plasma D-glucose and insulin concentrations, and D-glucose infusion rate during a hyperinsulinemic-euglycemic clamp were measured after 65 days exposure to exogenous fructose and either olive oil- or guar-enriched diet. The results were compared to those previously collected in control animals exposed for the same period to either tap water or the fructose-containing drinking water and a standard diet. Diet supplementation with olive oil or guar failed to affect the increase in the insulinogenic index and the decrease in insulin sensitivity and fasted/fed ratio for plasma insulin concentration caused by exogenous fructose. In the rats exposed to exogenous fructose, the olive oil-fed rats differed from other animals by the absence of a decrease in food intake and body weight gain, whilst the guar-fed rats differed from other animals in a lower plasma D-glucose concentration in fed state and an absence, at day 65, of a higher plasma D-glucose concentration than that at day 0 measured in after overnight fasting state. These findings argue in favour of guar, rather than olive oil, to oppose the effect of exogenous fructose on glucose homeostasis.

Fatty acid content and pattern of epididymal and parametrial adipose tissue lipids in streptozotocin (type 1) and Goto-Kakizaki (type 2) diabetic rats

Attention was recently drawn to differences in the fatty acid pattern of liver phospholipids and triglycerides in animal models of type 1 and type 2 diabetes. The present study extends this knowledge to epididymal or parametrial adipose tissue lipids. The fatty acid pattern of such lipids was established in four fed female normal rats, four overnight fasted female normal rats, six fed female rats rendered diabetic by an injection of streptozotocin 3 days before sacrifice (STZ rats), and four female and four male Goto-Kakizaki rats (GK rats) also examined in the fed or fasted state. In addition to the fasting-induced and diabetes-related changes in plasma D-glucose and insulin concentrations, differences in either the weight percentage of fatty acids or the paired ratio between distinct fatty acids were often encountered. For instance, in the GK rats, gender differences were observed in the weight percentage of C18:2omega6, as well as C18:2omega6/C18:3omega6, C18:3omega6/C20:4omega6, C20:5omega3/C22:5omega3 and C22:5omega3/C22:6omega3 ratios. When compared to normal rats, the activity of Delta9-desaturase was markedly increased in GK rats and, to a lesser extent, in STZ rats. Starvation also increased to some extent the activity of Delta9-desaturase. The relative content of C22:6omega3 was also higher in diabetic than in normal rats. Further differences between GK and STZ rats concerned the generation of C18:3omega6 from C18:2omega6, C20:4omega6 from C18:3omega6, and C20:5omega3 from C18:3omega3. Several differences found in the adipose tissue of GK versus STZ rats were reminiscent of those recently identified in the liver triglycerides of these two types of diabetic animals, suggesting a common regulatory mechanism, possibly linked to the higher insulinemia of GK rats versus STZ rats.

Hyperglycemia-induced changes in hepatic membrane fatty acid composition correlate with increased caspase-3 activities and reduced chick embryo viability

Fertile chicken eggs were injected with various concentrations of either d-glucose or l-glucose during the first three days of embryonic development. The exogenous glucose concentrations ranged from 0 to 18.58 μmol/kg egg. At 18 days of development (theoretical stage 44), brains, livers, and blood from chorio-allantoic vessels were isolated from living embryos. Exogenous d-glucose and l-glucose caused increased plasma d-glucose levels, increased plasma alanine aminotransferase (ALT) activities, and decreased embryo viability. Embryo viability was monitored by a reduction in the percentage of living embryos at theoretical stage 44, reduced embryo masses, reduced brain masses, and reduced liver masses. When compared to controls, embryonic exposure to either exogenous d-glucose or l-glucose caused increased caspase-3 activities and increased lipid hydroperoxide (LPO) levels in both brain and liver tissues. Because lipid hydroperoxides are lipid peroxidation intermediates that result in the attack of any unsaturated neutral lipid or unsaturated phospholipid, the effect of exogenous glucose on hepatic membrane fatty acid composition was studied. Exogenous glucose (either d-glucose or l-glucose) promoted reduced levels of several unsaturated, long-chain fatty acids and increased levels of saturated, short-chain fatty acids within hepatic membranes. Exogenous-glucose induced decreases in the ratios of unsaturated/saturated fatty acids and long-chain/short-chain fatty acids within hepatic membranes which strongly correlated with glucose-induced increases in plasma ALT activities and moderately correlated to hepatic LPO levels. These observations are consistent with the hypothesis that embryonic hyperglycemia promotes hepatic membrane lipid peroxidation and hepatic cell death.

Effects of an Olive Oil–Enriched Diet on Plasma GLP-1 Concentration and Intestinal Content, Plasma Insulin Concentration, and Glucose Tolerance in Normal Rats

The present study aims mainly at measuring, in normal rats, the GLP-1 response to oral intake of an olive oil-enriched diet (OO), and at assessing the long-term effects of such a diet on the GLP-1 content of the intestinal tract, as well as the plasma D-glucose, insulin, and GLP-1 pattern during an oral glucose tolerance test. In meal-trained rats, the mean increment in plasma GLP-1 concentration at min 10 and 20 was 1.39 +/- 0.23 ng/mL higher (p < 0.001) in the rats given access to the OO diet rather than control diet. Relative to the initial value (d 0), the gain in body weight at d 50 was also higher in the animals fed the OO rather than control diet. At d 50, the GLP-1 content of the jejunum, ileum, colon, and cecum were not significantly different in the two groups of rats. At d 19 and 36, the increment in both plasma insulin concentration and paired ratio between plasma insulin and D-glucose concentrations were again higher, during an oral glucose tolerance test conducted in overnight fasted animals, in the rats otherwise fed the OO, as distinct from control, diet. The intake of an olive oil-enriched diet thus increases, in normal rats, GLP-1 release, this coinciding during long-term exposure to the OO diet with higher body weight gain, increased secretory response of insulin-producing cells to oral glucose administration, and, after 36 d, improved glucose tolerance.

Plasma D-Glucose, D-Fructose and Insulin Responses after Oral Administration of D-Glucose, D-Fructose and Sucrose to Normal Rats

Objective: To assess whether oral D-fructose modifies the plasma D-glucose and insulin responses to oral D-glucose administration in normal rats.Design: Oral D-glucose (1.7, 3.5, 6.9 or 13.9 μmol/g body weight), D-fructose (6.9 μmol/g), both D-glucose and D-fructose (1.7 or 3.5 μmol/g of each hexose) or sucrose (3.7 μmol/g) were administered intragastrically to overnight fasted rats and the plasma concentration of D-glucose, D-fructose and insulin measured over the ensuing 120 minutes. Control experiments were conducted after oral administration of H2O or saline.Results: The administration of D-fructose, given as the free hexose or as sucrose, instead of augmenting the plasma D-glucose concentration evoked by the concomitant administration of D-glucose, tended both to improve the insulin response of the pancreatic B-cell and to minimize hyperglycemia, when compared to the results of experiments including the administration of equimolar amounts of D-glucose alone. For instance, the area under the plasma D-glucose curve was comparable in the rats receiving both D-glucose and D-fructose (3.5 μmol/g of each hexose) and the rats receiving only D-glucose (3.5 μmol/g), averaging respectively 836 ± 32 and 850 ± 34 mM · min each. Likewise, the paired ratio between the areas under the plasma insulin and D-glucose curves, when corrected for the threshold concentration for the insulinotropic action of the hexose (2.05 ± 0.10 mM), averaged 44.3 ± 3.0 nmol/mol in the 16 rats receiving D-fructose alone, sucrose alone or both D-glucose and D-fructose, as compared to 37.7 ± 2.9 nmol/mol in the 22 rats receiving increasing amounts of D-glucose alone.Conclusions: The intake of D-fructose, as the free hexose or as sucrose, favours D-glucose homeostasis. This is likely to be attributable to the reciprocal effects of the aldose and ketose upon their respective phosphorylation by glucokinase in both hepatocytes and insulin-producing pancreatic islet cells.

Pharmacodynamics, insulinotropic action and hypoglycemic effect of nateglinide and glibenclamide in normal and diabetic rats

Control and streptozotocin-induced diabetic rats, as well as GK rats, received a single oral administration of either nateglinide (50 microg/g body wt.) or glibenclamide (1.0 microg/g body wt.). The plasma D-glucose and insulin concentrations, as well as the content of plasma, liver and pancreas in either nateglinide or glibenclamide were measured 60 min or 24 hours after the administration of these antidiabetic agents. At the 60th min, the plasma, hepatic and pancreatic content of nateglinide largely exceeded that of glibenclamide. At the 24th hour, however, the plasma concentration, as well as liver and pancreas content, of nateglinide became negligible, whilst that of glibenclamide exceeded the values recorded at the 60th min. A comparable pattern characterized the insulinotropic action and hypoglycemic effect of these two antidiabetic agents. This study thus emphasizes the vastly different pharmacodynamics of nateglinide and glibenclamide in both control and diabetic rats.

Metabolism of D-[3-3H]glucose, D-[5-3H]glucose, D-[U-14C]glucose, D-[1-14C]glucose and D-[6-14C]glucose in pancreatic islets in an animal model of type-2 diabetes

This study aims at exploring specific aspects of D-glucose metabolism, so far not yet investigated, in pancreatic islets from adult control rats and animals (STZ rats) injected with streptozotocin during the neonatal period. The latter animals, which represent a current model of type-2 diabetes, displayed a lower body weight, higher plasma D-glucose concentration and lower insulinogenic index than control rats. The protein, DNA and insulin content were all also lower in islets prepared from STZ, rather than control rats. In the presence of 10.0 mM D-glucose, the paired ratio between D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization was also decreased in the islets from STZ rats. No significant difference between control and STZ rats was observed, however, in terms of the ratios between D-[3-3H]glucose and D-[5-3H]glucose utilization, between the generation of radioactive lactate from 14C-labelled D-glucose and tritiated D-glucose utilization and between D-[1-14C]glucose and D-[6-14C]glucose oxidation. These findings reinforce the view that the previously documented preferential impairment of the oxidative modality of glycolysis in islets from STZ rats contrasts with the absence of any major anomaly in other variables of D-glucose catabolism.

Invertase, maltase, lactase, and peroxidase activities in duodenum of BB rats.

The development of immune-mediated diabetes in BB rats may involve a defect of the gastrointestinal tract (GI), as suggested by increased gut permeability. This study aimed at measuring invertase, maltase, lactase, and peroxidase activities in the duodenum of diabetesprone BioBreeding (BBdp) rats and control BioBreeding rats (BBc) given free access to NIH-07 diet up to the time of killing at 60 66 d of age. After washing the entire small intestine, the duodenal mucosa was scraped off in the first 5-cm segment from the pylorus and frozen in distilled water. Invertase, maltase, and lactase activities were measured by monitoring the conversion of [U-(14)C]sucrose, [U-(14)C]maltose, and [D-[1-(14)C]glucose] lactose to radioactive hexoses, which were phosphorylated in the presence of adenosine triphosphatase and yeast hexokinase and then separated from their precursor by ion-exchange chromatography. Peroxidase activity was measured by a spectrophotometric procedure. In the BBdp rats, the activity of invertase, maltase, and lactase averaged, respectively, 70.2 +/- 4.4, 81.2 +/- 4.3, and 75.7 +/- 4.1% (n = 16 and p < 0.001 in all cases) of the control values found in BBc rats of the same sex. Inversely, after exclusion of two female BBc rats with abnormally high plasma D-glucose concentration, the activity of peroxidase in the BBdp rats averaged 157.4 +/- 20.0% (n = 16; p < 0.02) of the mean control value recorded in BBc rats of the same sex (100.0 +/- 9.3%; n = 14). These findings are compatible with the view that a proinflammatory state of the GI associated with compromise function may precede the occurrence of pancreatic insulitis in BBdp rats and, possibly, human subjects with type 1 diabetes.

Cerebral glucose transport implies individualized glial cell function.

Previous positron emission tomography (PET) measurements of cerebral glucose transport using [11C]-3-O-methylglucose (CMG) suggested an interindividual variation in the values of the rate constant of tracer outflow (k2) larger than that for the clearance rate of inflow (K1). These two parameters were examined in healthy cerebral cortex by dynamic PET in 4 men and 2 women (aged 24 to 73 years) without neurologic disease, and in 1 man (42 years) with a recent left hemispheric cerebral infarction under normoglycemia (average blood plasma d-glucose concentration, 5.44 +/- 1.94 micromol/mL) and again under hyperglycemia (average, 10.24 +/- 1.44 micromol/mL). Time-radioactivity curves were obtained from healthy cortex (grey matter) and plasma and analyzed for the values of K1 and k2 by two graphical approaches and two fitting procedures. Both K1 and k2 significantly declined with increasing plasma glucose levels. A highly significant interindividual but not intraindividual variability for k2 was found at normoglycemia and hyperglycemia. The interindividual variability of K1, although borderline significant, was less than that of k2. Accordingly variable were the distribution volumes K1/k2. These data suggest individualized glial cell function and may be relevant to pathogenesis of neuropsychiatric disease.

Potentiation by methyl pyruvate of GLP-1 insulinotropic action in normal rats

Methyl pyruvate (MP) stimulates insulin release both in vivo and in vitro. The present study aims at investigating whether MP is also able to enhance the B-cell secretory response to glucagon-like peptide 1 (GLP-1). In anaesthetized rats receiving a primed constant infusion of MP, the ester augmented plasma insulin concentration before GLP-1 injection and potentiated the insulinotropic action of the intestinal hormone. MP infusion also augmented plasma D-glucose concentration, whether in the absence or presence of GLP-1. A further rise in plasma D-glucose concentration was observed when the infusion of MP was halted, this coinciding with a fall in plasma insulin concentration. Whilst documenting that MP indeed enhances the B-cell secretory response to GLP-1, these findings do not suggest that MP is an appropriate tool for optimizing the hypoglycaemic action of the enteric hormone in the treatment of type-2 diabetes mellitus.

Dietary effects on insulin and nutrient metabolism in mesenteric lymph node cells, splenocytes, and pancreatic islets of BB rats

The present studies were performed to determine if a protective diet has different effects on the metabolic activity or function of islet cells, as well as the metabolic activity of mesenteric lymph node (MLN) cells and spleen cells, from BioBreeding (BB) rats. Diabetes-prone BB (BBdp) rats and control non–diabetes-prone BB (BBc) rats were fed for about 20 days either a mainly plant-based diabetogenic diet, NIH-07 (NIH), or a protective semipurified diet with hydrolyzed casein (HC) as the amino acid source. At 6 to 8 weeks of age, BBdp rats had high plasma D-glucose and low insulin concentrations, low insulin content, and low metabolic and secretory responses to D-glucose in isolated pancreatic islets. Islet metabolism, as measured by accumulation of 14C-acidic metabolites, amino acids, and the ratio of D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization was increased in control rats fed HC (P < .05); a similar trend in BBdp rats was not significant. Feeding the HC diet increased islet insulin content (P < .01) by 13% in BBdp and 23% in BBc rats; other metabolic and hormonal variables were unaffected. Compared with BBc rats, BBdp rats displayed higher rates of L-[U-14C]glutamine oxidation, D-[5-3H]glucose utilization, and D-[U-14C]glucose oxidation in MLN cells, but not in splenocytes. There was a dramatic decrease of L-[U-14C]glutamine oxidation in MLN cells from BBc and BBdp rats fed HC. Glycolysis was decreased in control rats. We conclude that the protection afforded by feeding BBdp rats a HC diet is associated with increased insulin in target β cells and downregulation of metabolic activity in gut-associated MLN cells. Metabolic activity in splenocytes, cells representative of the systemic immune system, was less affected. These data suggest that diet-induced metabolic changes occur in the islets and nearby cells of the gut immune system in the period before classic insulitis. Changes in the islets were smaller in comparison to the dramatic remodeling of nutrient catabolism in MLN cells. MLN downregulation may reflect baseline metabolic activity in the absence of diabetogenic (or other) food antigens and further highlights an important interaction between diabetogenic food antigens and the gut immune tissues.

Effects of succinate dimethyl ester on the metabolic and hormonal response to exercise in fed and starved rats.

This study aims at investigating the possible beneficial effect of succinic acid dimethyl ester (SAD), injected intraperitoneally (5.0 micromol/g body wt.), upon the metabolic and hormonal response to a 60 min exercise in both fed and overnight starved rats. In fed rats, the injection of SAD minimized the fall in plasma D-glucose concentration, and the increase in plasma lactate, beta-hydroxybutyrate, free fatty acid and glycerol concentrations, otherwise provoked by exercise. SAD, however, failed to prevent the decrease in plasma insulin concentration and liver glycogen content caused by exercise. Starved rats displayed lower plasma D-glucose and insulin concentrations and higher plasma beta-hydroxybutyrate and free fatty acid concentrations than fed rats. The body weight, liver weight and paraovarian fat weight, as well as the glycogen content of both liver and heart were also decreased in the starved rats. In the latter animals, the injection of SAD again opposed the exercise-induced increase in plasma beta-hydroxybutyrate, free fatty acid and glycerol concentrations, and again failed to prevent the more modest decreases in plasma insulin concentration and liver glycogen content caused by exercise in the starved, as distinct from fed rats. These findings suggest that, independently of any obvious change in plasma insulin concentration, SAD minimizes the exercise-induced mobilization and enhanced utilization of endogenous nutrients, especially fatty acids and glycerol produced by hydrolysis of triglycerides in adipose tissue, presumably through its capacity to act as an oxidizable nutrient in various cell types and as a gluconeogenic precursor in hepatocytes.

Effects of a Protective Hydrolyzed Casein Diet upon the Metabolic and Secretory Responses of Pancreatic Islets to IL-1β, Cytokine Production by Mesenteric Lymph Node Cells, Mitogenic and Biosynthetic Activities in Peyer's Patch Cells, and Mitogenic Activity in Pancreatic Lymph Node Cells from Control and Diabetes-Prone BB Rats

The effects of substituting a plant-based control diabetogenic diet (NIH diet) by a protective hydrolyzed casein diet (HC diet) upon selected metabolic and functional variables were recently investigated in Peyer's patch cells, splenocytes, mesenteric lymph node cells, and pancreatic islets from either control (BBc) or diabetes-prone (BBdp) BB rats. In the present work, the plasma d-glucose and insulin concentrations, the protein and insulin content of pancreatic islets, the metabolism of d-glucose, and its insulinotropic action in islets first cultured for 24 h in the absence or presence of IL-1β, the production of IFN-γ and IL-10 by mesenteric lymph node cells cultured for 48 h in the absence or presence of concanavalin A, the mitogenic activity of Peyer's patch cells and pancreatic lymph node cells in the absence or presence of the same lectin, and the biosynthetic activity of Peyer's patch cells were measured in the BBc and BBdp rats fed either the NIH or the HC diet. Two major novel findings emerged from this study. First, in immune cells, diet HC increased to a greater extent the responsiveness to concanavalin A of certain metabolic and functional variables in BBdp rats than in BBc rats. Second, pancreatic islet cells of BBdp rats were less sensitive to IL-1β than those of BBc rats and this difference was further accentuated when the animals were fed the HC rather than the NIH diet. These findings afford further support to the view that, in BB rats, changes in the biological behavior of Peyer's patch cells, mesenteric and pancreatic lymph node cells, and pancreatic islet cells participate in the pathogenesis of insulin-dependent diabetes mellitus and its prevention by a suitable dietary manipulation.

Metabolic and Secretory Response to [formula omitted]-Fructose in Pancreatic Islets from Adult Rats Injected with Streptozotocin during the Neonatal Period

The metabolic and secretory responses to d-glucose and/or d-fructose were measured in pancreatic islets prepared from either control rats or animals that had been injected with streptozotocin during the neonatal period (STZ rats). The STZ rats displayed higher plasma d-glucose concentrations, but lower plasma insulin concentrations, islet insulin content, as well as basal and nutrient-stimulated insulin release. This coincided with lower rates of d-[U-14C]hexose oxidation and d-[5-3H]hexose utilization. In both control and STZ rats, d-fructose failed to affect significantly the metabolism of d-glucose, while the aldohexose increased the ratio between d-[U-14C]fructose oxidation and d-[5-3H]fructose conversion to 3HOH. Such a ratio was higher than that found with radioactive d-glucose in islets exposed to both hexoses, whether in control or STZ rats, indicating a far-from-negligible contribution of fructokinase to the phosphorylation of d-fructose. Despite these analogies between both the respective fate of d-glucose and d-fructose and the reciprocal metabolic effects of the two hexoses in islets from control and STZ rats, the secretory response to the ketohexose in islets from STZ rats was preferentially suppressed, relative to that evoked by the aldohexose. This gives support to the idea that the insulinotropic action of d-fructose may not be entirely accounted for by its nutritional value in islet cells.

Assessment of the Nutritional Value of Glycerol-1,2,3-tris(methylsuccinate) in Fed and Starved Rats

The nutritional value of glycerol-1,2,3-tris(methylsuccinate), a novel ester of succinic acid with high insulinotropic efficiency both in vitro and in vivo, was assessed in both fed and starved rats. The infusion of the ester, given in a daily amount (1.2 μmol · g body wt−1) well in excess of what could result from its repeated intravenous administration as an insulinotropic agent in non-insulin-dependent diabetes (0.07 μmol · g body wt−1 for each administration), failed to prevent the fall in body weight, liver and muscle glycogen contents, and plasma d-glucose or insulin concentration, as well as the increase in plasma free fatty acid and β-hydroxybutyrate concentrations caused by starvation. The sole indications that the ester may serve, to a limited extent, as an alternative nutrient in starved rats consisted in a somewhat higher weight of both liver and paraovarian adipose tissue and somewhat higher activity of liver glucokinase in rats receiving the ester than in animals infused with saline. The low nutritional value of this ester thus answers the objection of its possible role as an extrapancreatic nutrient or gluconeogenic precursor in the perspective of its use as an insulinotropic tool in type 2 diabetes.

Effect of dehydroepiandrosterone in hereditarily diabetic rats.

Goto-Kakizaki rats (GK rats) were given access for 4 weeks to a diet enriched with dehydroepiandrosterone (DHEA, 0.2 per cent, w/w). The incorporation of DHEA in the food failed to affect significantly body growth, plasma D-glucose and insulin concentrations, pancreatic islet insulin content or the activity of both mitochondrial glycerophosphate dehydrogenase (mGDH) and NADP-malate dehydrogenase (malic enzyme) in islet homogenates. DHEA however, increased the activity of mGDH and, at least in male rates, that of the malic enzyme also in the liver. It lowered the abnormally high basal insulin release otherwise found in the islets from diabetic rats, and, as judged from the ratio of insulin output at 16.7 mM/2.8 mM D-glucose, improved the cell responsiveness to the hexose. This coincided with a decreased plasma insulin/D-glucose ratio, suggesting that the major effect of DHEA was to increase the sensitivity to insulin of extrapancreatic targets, thus resulting in a secondary improvement of cell secretory behaviour.

Nutritional value of succinic acid monoethyl ester in starvation.

Rats were fasted for 48 h, but infused with either NaCl or the sodium salt of monoethyl succinic acid (EMS), both delivered at a rate of 80 mumol/g body weight per day. The infusion of EMS, as compared to NaCl, failed to affect paraovarian adipose tissue or liver weight, liver or muscle glycogen, and insulinemia. It accentuated the starvation-induced fall in body weight, and decreased both liver and muscle protein content. Nevertheless, the succinate ester increased plasma D-glucose concentration, delayed the rise in ketonemia, maintained a higher glucokinase/hexokinase activity ratio in liver and pancreatic islets, and allowed for a more efficient stimulation of insulin release by D-glucose or 2-ketoisocaproate in isolated pancreatic islets. These findings indicate that monoethyl succinate displays a significant nutritional value when infused in starved rats.

Transplantation of β cells from transgenic mice into nude athymic diabetic rats restores glucose regulation

We have shown that elevated plasma d-glucose levels in experimentally-induced diabetic nude athymic rats can be reduced by intraperitoneal transplantation of microcarrier-attached insulin producing β cells from the mouse pancreatic β cell line, β TC-1. The reduction in the level of hyperglycemia was observed as early as two days following cell transplantation and was associated with a concomitant increase in plasma insulin levels. β TC-1 cell transplanted diabetic rats had plasma d-glucose levels similar to those found in non-diabetic control animals and remained normoglycemic throughout the 39 day experimental period. The β TC-1 cell transplanted diabetic rats also had near normalization of body weight, food and water intake and of urine output when compared to control diabetic and non-diabetic rats. Similarly, they exhibited improved blood glucose clearance following intravenous d-glucose administration. These results suggest that β TC-1 cells regulate d-glucose homeostasis following transplantation into diabetic rat recipients in a manner similar to that of endogenous pancreatic β cells.