Insulin Concentrations In Rats Research Articles

The experimental model of type 2 diabetes mellitus caused by a high-fat diet with low-dose streptozotocin in rats

Aim . To develop a pathogenetically reasonable model of type 2 diabetes with marked peripheral insulin resistance and relative insulin deficiency in rats using a high-fat diet and a single injection of streptozotocin in the low dose. Materials and methods. Experiments were conducted on 16 outbred male rats. Type 2 diabetes model in experimental animals was achieved by feeding them with high-fat diet (55% of energy from fat) for 28 days followed by a single injection of streptozotocin (35 mg/kg). The serum glucose and insulin concentrations in rats were measured before streptozotocin administration and at the end of the experiment. To estimate insulin resistance, insulin tolerance test and glucose tolerance test were performed. Total protein, albumin, total and direct bilirubin, urea, uric acid, total cholesterol, high-density lipoproteins and low-density lipoproteins, and activity of alanine aminotransferase and aspartate aminotransferase were measured in the blood serum. Results . A high-fat diet with a single injection of streptozotocin resulted in lipid and protein metabolism disorders and peripheral tissues insulin resistance in experimental animals. Basal insulin levels did not change against the backdrop of high glucose level. Conclusions . These results indicate that feeding rats with a high-fat diet (55% of calories from fats) and a single administration of streptozotocin at a low dose (35 mg/kg) reproduce general pathological processes of type 2 diabetes. This model can be used to study the pathogenesis of type 2 diabetes as well as to investigate the effect of potential hypoglycemic agents.

An Alteration in the Cecal Microbiota Composition by Feeding of 1-Kestose Results in a Marked Increase in the Cecal Butyrate Content in Rats.

Functional food ingredients, including prebiotics, have been ardently developed for improving the intestinal environment. Fructooligosaccarides (FOS), including fructans, are the well researched and commercialized prebiotics. However, to our knowledge, few studies have been conducted on the physiological effects of each component of FOS as prebiotics. 1-Kestose, a component of FOS, is composed of one glucose and two fructose molecules, and is considered as a key prebiotic component in short-chain FOS. In the present study, we examined the effects of dietary 1-kestose using 0.5–5% 1-kestose diets on cecal microbiota composition and cecal contents of short-chain fatty acids and lactate in rats. The findings indicate that dietary 1-kestose induced cecal hypertrophy and alterations in the cecal microbiota composition, including a marked increase in the cell number of Bifidobacterium spp. These alterations were associated with significant increases in acetate and lactate, and a marked increase in butyrate in cecal contents. Furthermore, dietary 1-kestose induced a significant decrease in serum insulin concentration in rats fed 2.5–5% 1-kestose diet. These findings suggest a potential of 1-kestose to be a prebiotic for improving the metabolism of the host.

The impact of iron content in a diet high in fat, fructose, and salt on metabolic state and mineral status of rats

The purpose of the study was to assess the influence of dietary iron content on lipid and carbohydrate metabolism and on zinc and copper status in rats fed with a diet high in fat, fructose, and salt. Wistar rats were fed with diets high in fat, fructose, and salt, containing differing amounts of iron, namely, deficit, normal, and high levels. After 6 weeks, the animals were weighed and killed. The liver, heart, and pancreas were collected, as were blood samples. The total cholesterol, triglycerides, fasting glucose, and insulin levels in the serum were measured. The iron, zinc, and copper concentrations in tissues and serum were determined. It was found that in rats fed with the iron-deficit diet, cholesterol and glucose profiles improved. Both deficit and excess iron in the diet decreased insulin concentration in rats and disturbed iron, zinc, and copper status. High-iron level in the diet decreased the relative mass of the pancreas. In conclusion, the decrease in serum insulin concentration observed in rats fed with the modified diet high in iron was associated with iron and copper status disorders, and also, with a relatively diminished pancreas mass. A deficit of iron in the diet improved lipid and carbohydrate metabolism in rats.

Chronic stress and carbohydrate metabolism: Persistent changes and slow return to normalcy in male albino rats

The present study tested the hypothesis that long-term repeated exposure to stressors results in irreversible changes in carbohydrate metabolism. Groups of adult male rats (five per group) were restrained for 1 h and 4 h later were forced to swim for 15 min everyday for 2, 4, or 24 weeks; five rats were autopsied after each interval. Groups of five rats exposed to stress for 2 or 4 weeks were maintained without further treatment (recovery groups) for up to 24 weeks. The fasting blood glucose concentration, measured at weekly intervals, was significantly higher in the stressed rats than in controls throughout the experiment, except in the 24th week, whereas that of the recovery groups was significantly higher than controls only up to the 8th week after the end of stress exposure and then reached normalcy. The blood concentrations of glucose, lactate, and pyruvate were significantly higher in the 2 and 4 weeks stress groups than in controls, whereas, except for lactate, in rats stressed for 24 weeks these values did not significantly differ from those in controls. These changes were accompanied by increased gluconeogenesis and glycogenolysis as shown by alterations in activities of hepatic carbohydrate metabolizing enzymes and unaltered blood insulin concentrations in rats stressed for 2, 4, and 24 weeks. Furthermore, the blood insulin levels did not significantly vary among controls and the 2, 4, and 24 weeks stress groups. The results reveal that though hyperglycemia induced by long-term stress exposure is reversible, it persists for a prolonged period, even after the termination of stress exposure, before reaching normalcy. Prevalence of hyperglycemia for a prolonged period through increased activities of hepatic enzymes in stressed rats exemplifies allostasis.

Micronutrients in Parenteral Nutrition: Boron, Silicon, and Fluoride

Boron may be beneficial for bone growth and maintenance, central nervous system function, and the inflammatory response, and silicon may be beneficial for bone maintenance and wound healing. Fluoride is not an essential element but amounts provided by contamination may be beneficial for bone strength. Fluoride toxicity may be a concern in parenteral nutrition. Further studies are warranted to determine whether there are optimal amounts of boron and silicon that should be delivered to typical and special population patients receiving parenteral nutrition. In addition, further studies are needed to determine whether providing the dietary guideline of adequate intake amounts of fluoride parenterally would prevent or treat parenteral nutrition osteopenia.

Polyglycolic Acid-Islet Grafts Improve Blood Glucose and Insulin Concentrations in Rats With Induced Diabetes

Pancreatic islet transplantation is a promising therapeutic treatment for type 1 diabetes mellitus. In the present study, we cocultured islets with or without a polyglycolic acid (PGA) fibrous scaffold for 5 days and transplanted the PGA-islet grafts into the leg muscles of Wistar rats with streptozotocin-induced diabetes; controls were injected with saline. The results showed that the blood glucose concentrations of the group given islets embedded with the PGA scaffold were lower than those without the scaffold or controls. On the other hand, the insulin content of the PGA-islet group was higher at all 5 time points compared with the insulin contents of the other 2 groups. After transplantation, many islets in the PGA-islet grafts showed normal morphology (as seen under the scanning electron microscope) and were surrounded by red blood cells. A fibrous extracellular matrix was visible around the PGA-islet grafts. These results demonstrated that PGA-islet grafts improved blood glucose and insulin concentrations in rats with induced diabetes.

Peripheral administration of CDP-choline and its cholinergic metabolites increases serum insulin: Muscarinic and nicotinic acetylcholine receptors are both involved in their actions

The present study was designed to test the effects of CDP-choline and its metabolites on serum insulin concentrations in rats and to investigate the involvements of cholinergic and adrenergic receptors in the effect. Intraperitoneal (i.p.) administration of CDP-choline (200–600 μmol/kg) increased serum insulin in a dose- and time-related manner. Equivalent doses (200–600 μmol/kg; i.p.) of phosphocholine or choline also increased serum insulin dose-dependently. Serum-free choline concentrations increased several-fold following i.p. administration of CDP-choline, phosphocholine or choline itself. In contrast, equivalent doses of cytidine monophosphate and cytidine failed to alter serum insulin concentrations. The increases in serum insulin induced by i.p. 600 μmol/kg of CDP-choline, phosphocholine or choline were abolished by pretreatment with the ganglionic nicotinic acetylcholine receptor antagonist hexamethonium (15 mg/kg; i.p.), or by the muscarinic receptor antagonist atropine methylnitrate (2 mg/kg; i.p.). Pretreatment with prazosin (0.5 mg/kg; i.p.), an α 1-adrenoceptor antagonist, or yohimbine (5 mg/kg, i.p.), an α 2-adrenoceptor antagonist, enhanced slightly the increases in serum insulin in response to 600 μmol/kg of CDP-choline, phosphocholine and choline. Serum insulin also increased following central administration of choline; the effect was blocked by intracerebroventricularly injected atropine, mecamylamine or hemicholinium-3 (HC-3). It is concluded that CDP-choline or its cholinergic metabolites phosphocholine and choline increases circulating insulin concentrations by increasing muscarinic and nicotinic cholinergic neurotransmission in the insulin secreting β-cells.

A1adenosine receptor partial agonist lowers plasma FFA and improves insulin resistance induced by high-fat diet in rodents

There is substantial evidence in the literature that elevated plasma free fatty acids (FFA) play a role in the pathogenesis of type 2 diabetes. CVT-3619 is a selective partial A(1) adenosine receptor agonist that inhibits lipolysis and lowers circulating FFA. The present study was undertaken to determine the effect of CVT-3619 on insulin resistance induced by high-fat (HF) diet in rodents. HF diet feeding to rats for 2 wk caused a significant increase in insulin, FFA, and triglyceride (TG) concentrations compared with rats fed chow. CVT-3619 (1 mg/kg) caused a time-dependent decrease in fasting insulin, FFA, and TG concentrations. Acute administration of CVT-3619 significantly lowered the insulin response, whereas glucose response was not different with an oral glucose tolerance test. Treatment with CVT-3619 for 2 wk resulted in significant lowering of FFA, TG, and insulin concentrations in rats on HF diet. To determine the effect of CVT-3619 on insulin sensitivity, hyperinsulinemic euglycemic clamp studies were performed in C57BL/J6 mice fed HF diet for 12 wk. Glucose infusion rate was decreased significantly in HF mice compared with chow-fed mice. CVT-3619 treatment 15 min prior to the clamp study significantly (P < 0.01) increased glucose infusion rate to values similar to that for chow-fed mice. In conclusion, CVT-3619 treatment lowers FFA and TG concentrations and improves insulin sensitivity in rodent models of insulin resistance.

Reduction of Mammary and Liver Lipogenesis and Alteration of Milk Composition during Lactation in Rats by Hypothyroidism

The profound impairment in litter growth produced by untreated maternal hypothyroidism (HypoT) may be a consequence of maternal metabolic dysfunctions affecting lactation. In this work we studied the effects of HypoT on mammary and liver lipid metabolism and its consequences on milk quality. We studied the effects of prolonged 6-propyl-2-thiouracil (PTU)-induced HypoT (0.01% PTU in drinking water starting 8 days before mating until sacrifice) on milk macronutrient composition, liver and mammary lipid metabolism and content and serum lipid, and glucose and insulin concentrations in rats on days 7, 15 (L15), and 20 (L20) of lactation. Mammary and hepatic mRNA abundances of lipogenic enzymes were measured using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on L15 and L20. Milk lactose and triglycerides (TG) were reduced by HypoT, as well as mammary acetyl CoA carboxylase (ACC) activity on L15 and L20, and ACC and lipoprotein lipase (LPL) mRNA on L20. HypoT also decreased hepatic ACC activity on both days, ACC mRNA on L15 and liver [(3)H]H(2)O incorporation to TGs and TG content on L20. HypoT diminished insulinemia, increased serum total lipids, and decreased serum TGs on some or all the days of lactation studied. HypoT produces a drastic decrease in milk TGs; the main cause for this seems to be the decreases in liver TG synthesis and in circulating TGs, which, along with reduced mammary uptake of fatty acids caused by decreased LPL expression and possibly diminished mammary lipogenesis, result in an impaired mammary output of TGs to the milk. Thus, the impaired growth of the litters of HypoT mothers can be largely attributed to the low milk quality along with the impaired milk ejection.

高等植物起源のＦｒｕｃｔｏｓｙｌｔｒａｎｓｆｅｒａｓｅの利用を目的とした遺伝子のクローニング

Recently, we have investigated enzymic production of non-digestible oligosaccharides which have several functional activities as “tertiary functional ingredients” of foods. Fructo-oligosaccharides synthesized from sucrose by Eurotium repense fructosyltransferase had the effect of no elevation of blood glucose or insulin concentrations in rats. Fructosylxyloside formed from sucrose and xylose with fructosyltransferase action of Scopulariopsis brevicaulis cells suppressed serum glucose and insulin responses and / or promoted the absorption of calcium and magnesium ions in rats administered with sucrose. On the other hand, we studied purification and characterization of several fructosyltransferases; sucrose: sucrose 1-fructosyltransferase (1-SST), fructan: fructan 1-fructosyltransferase (1-FFT) and a new enzyme, fructan: fructan 6G-fructosyltransferase (6G-FFT) from asparagus roots. Previously, we reported that the asparagus 1-FFT synthesized new functional oligosaccharides elongated with one or two additional fructose units by fructosyltransfer from 1-kestose to 4G-β-D-galactosylsucrose and the saccharides selectively stimulated growth for Bifidobacteria. In this study, we have tried the isolation and expression of cDNAs encoding 6G-FFT, 1-FFT and 1-SST from asparagus for industrial use. The cDNAs encoding 6G-FFT, 1-FFT and 1-SST were isolated from a cDNA library of asparagus leaves or roots. The isolated cDNAs were named AoFT 1, AoFT 2 and AoFT 3, respectively. The deduced amino acid sequences of these cDNAs showed a high homology with those of plant fructosyltransferases. Expression of these cDNAs was done using Pichia pastoris. The recombinant protein from Pichia transformed with AoFT 1 produced 1F,6G-di-β-D-fructofuranosylsucrose, neokestose and sucrose from 1-kestose, while the transformant with an empty vector produced no saccharides. These results show that 6G-FFT is expressed in P. pastoris. In the same way, recombinant protein from Pichia transformed with AoFT 2 produced nystose from 1-kestose and AoFT 3 recombinant protein produced 1-kestose from sucrose. These results also show that 1-FFT and 1-SST are expressed in P. pastoris. Three recombinant proteins had enzymatic properties similar to those of 6G-FFT, 1-FFT and 1-SST from asparagus roots, respectively.

Cooking attenuates the ability of high-amylose meals to reduce plasma insulin concentrations in rats.

Postprandial glycaemic control is important in the prevention and therapy of type 2 diabetes and related diseases. Agents that may reduce postprandial glycaemia and/or insulinaemia, such as consumption of high-amylose foods, are considered beneficial; however, little is known about the dose-response relationship and the effects of cooking. The aim of the present study was to define the dose-response curve for postprandial glycaemic and insulinaemic excursions following meals of different amylose content and to compare the dose-response curves for meals containing cooked and uncooked starches. Following an overnight fast, rats ingested a test meal and blood was sampled over 2 h. The meal was given at 1.0 g carbohydrate/kg body weight, with an amylose content of 0, 270, 600 or 850 g/kg total starch. The area under the glucose curve did not differ under any condition investigated. For the uncooked-starch diets, area under the insulin curve was higher for the 0 g amylose/kg total starch meal than all other meals (P=0.0001). For the cooked-starch diets, area under the insulin curve was higher in the 0 than the 600 and 850 g amylose/kg total starch groups (P<0.01), but did not differ from the 270 amylose/kg total starch group. These results suggest that even a relatively small proportion of uncooked amylose (270 g/kg total starch) is sufficient to achieve a maximal attenuating effect on postprandial insulin concentrations as compared with 0 g amylose/kg total starch. Following cooking, however, a much higher proportion of amylose (>or=600 g/kg total starch) is needed to achieve a similar effect.

Iodothyronines and insulin concentrations in rats of variable homozygosity, exposed to two types of stress

Iodothyronines and insulin concentrations in rats of variable homozygosity, exposed to two types of stress

Fetal growth, glucose tolerance and plasma insulin concentration in rats given a marginal-zinc diet in the latter stages of pregnancy.

1. Wistar rats were fed on a control semi-synthetic diet throughout pregnancy, or a control diet in the first 2 weeks and a marginal-zinc diet in the 3rd week of pregnancy. On day 20, after an overnight fast, half the animals in each group were given glucose by gavage and the 0-30 min rise in blood glucose measured in tail blood. After 60 min blood was taken by cardiac puncture for glucose and insulin assay. Maternal pancreases were removed and the Zn contents measured. Fetuses from each litter were combined for wet/dry weights, protein and DNA determinations. 2. Plasma insulin concentration was higher, and glucose concentration and pancreatic Zn content lower, in pregnant v. non-pregnant animals of similar age, fed on the same diet. Pancreatic Zn content was lowest in the marginal-Zn group of pregnant rats. Fetuses from mothers fed on the marginal-Zn diet during the last week of pregnancy were slightly heavier than controls and had a significantly higher protein: DNA ratio. The 0-30 min rise in blood glucose was significantly greater in the marginal-Zn animals. 3. In a second experiment, pregnant rats were given similar diets to those used in the first study, but the marginal-Zn diet was given for a shorter period (days 15-19 of pregnancy). On day 19 the rats were meal-fed and on day 20, after an overnight fast, an oral glucose dose was administered. Tail-blood was taken at timed intervals up to 60 min post-dosing for glucose assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Prolonged Starvation on Glycogen Synthase and Glycogen Synthase Phosphatase Activity in Rat Heart

Rats were fasted 24, 48 or 72 hours to determine the effect of several days without food on glycogen synthase and synthase phosphatase activity in heart. The basal percentage of synthase I decreased gradually from approximately 20% in fed animals to approximately 6% in rats starved for 72 hours. Glycogen increased progressively from 4.6 mg/g wet weight in fed rats to 7.6 mg/g wet weight in 72-hour starved rats. Thus, there was an inverse relationship between the glycogen concentration and the basal percentage of synthase I. The total synthase phosphatase activity measured at a standardized glycogen concentration decreased 50% by 24 hours of starvation and then was unchanged up to 72 hours. The 50% decrease in phosphatase activity correlated directly with insulin concentration in rats fasted 24–72 hours. The rapid stimulatory effect of insulin on synthase activity observed in fed rats was delayed in rats starved 24 and 48 hours. This correlated with a progressively slower synthase phosphatase response to insulin. The stimulatory effect of insulin was lost completely in 72-hour fasted rats. The proposed mechanism for the delayed response in rats starved 24 and 48 hours and lack of response in rats starved 72 hours is insulin resistance. The mechanism remains to be elucidated.

Effects of High Protein Diet on Insulin and Glucagon Secretion in Normal Rats

The effect of a high protein diet on blood glucose, insulin, and glucagon secretion was studied in the peripheral blood and isolated perfused pancreas of normal rats. A balanced diet (protein 27%, carbohydrate 61%, fat 12%) and a high protein diet (protein 55%, carbohydrate 30%, fat 15%) were given ad libitum to normal rats for 2 weeks. No significant difference in calorie intake or body weight changes were observed between the two groups. Fasting blood glucose and plasma insulin concentrations in rats fed the high protein diet were significantly higher than those in rats fed the balanced diet. The fasting plasma glucagon concentration, however, was the same in both groups. In the isolated perfused pancreas, the arginine-induced insulin secretion in rats fed the high protein diet was significantly higher than that in rats fed the balanced diet, whereas the arginine-induced glucagon secretion was not different in either group. The possible mechanism by which a high protein diet causes hypersecretion of insulin in vivo and in vitro are discussed.high protein diet insulin glucagon isolated perfused rat pancreas

Salicylate reduces serum insulin concentrations in the rat

Administration of sodium salicylate (50–500 mg/kg, i.p.) reduced serum insulin concentrations in nonfasted rats. This treatment also suppressed the rise in serum insulin that followed oral administration of glucose (by stomach tube) to fasted rats; this effect is only partly attributable to the blunted increase in serum glucose concentrations.