Significant Changes In Glucose Tolerance Research Articles

Effect of Aerobic Exercise Intervention on Renal Insulin Signaling Pathway in db/db Mice

Objective: To study the effects on insulin signaling pathway in db/db mice during aerobic exercise and discuss the related mechanisms. Methods: Ten BKS mice were selected as the quiet control group (WT group), and 20 BKS-db/db mice were randomly divided into two groups as the diabetic quiet control group (C group) and the diabetic simple exercise group (E group), with 10 mice in each group. The mice in E group were acclimatized to the low-intensity criterion (2~7m/min, 10min/day, 5 days/week) for one week, and then subjected to 8 weeks of aerobic endurance exercise training on a running platform (0° incline, 7~12m/min, 30~40min/day, 5 days/week), while the mice in groups WT and C were kept quietly. At the end of the experiment, the fasting blood glucose content, glucose tolerance, insulin tolerance of each group of mice were detected respectively, and the expression levels of AKT protein and insulin receptor protein were detected by Western Blot technique. Results: (1) Compared with the diabetic quiet control group (Group C), the glucose tolerance and insulin tolerance in the quiet control group (Group WT) showed significant changes (P＜0.05); in the diabetic simple exercise group (Group E), there was no significant change in glucose tolerance and insulin tolerance (P＞0.05). (2) Compared with the diabetic quiet control group (Group C), the expression level of insulin receptor protein was down-regulated (P<0.05) and AKT protein expression was up-regulated (P<0.05) in the diabetic simple exercise group (Group E); compared with the quiet control group (Group WT), the expression level of insulin receptor protein was increased (P<0.05) and AKT protein was decreased (P<0.05) in the diabetic quiet control group (Group C), expression level decreased (P<0.05). Conclusion: Exercise alone could not improve insulin resistance in db/db mice; eight weeks of aerobic exercise improved and corrected renal insulin signaling pathway and alleviated renal insulin resistance in db/db mice.

Resistant starch (RS), a novel endogenous inert marker for detecting glucose absorption of small intestine with sweeteners administration in mice

Resistant starch could be degraded by the fermentation of colonic microorganisms in the large intestine of mammals, but not in the small intestine. In this study, we established a novel strategy by using resistant starch as an endogenous marker to determine the glucose absorption of the small intestine of laboratory animals. By optimization of the classical enzymatic method of starch measurement, the demand for the sample weight was reduced by 90%. Moreover, the amount of resistant starch in normal feed was detectable without any extra addition. The value of small intestine glucose absorption of mice was similar when using resistant starch and titanium dioxide as inert markers. The fermentation of resistant starch by intestinal microorganisms in the small intestine was demonstrated not disturbing the detection of glucose absorption significantly. Artificial sweeteners exposed ICR mice showed different glucose absorption which indicated, first, resistant starch can be used as a novel endogenous marker in the small intestine of small animals; second, although glucose tolerance did not change in mice after short-term exposure to artificial sweeteners, there were significant changes in glucose absorption associated with it; third, the short-term exposure resulted in no significant change in glucose tolerance.

Weight Loss With a Novel Peptide YY Analogue for Obesity: A Randomised, Placebo-Controlled Phase I Trial

Abstract Background: Obesity and its co-morbidities remain a prime driver of global morbidity and mortality. Current therapies for obesity are limited in efficacy and durability, have serious adverse effects or are not scalable to the numbers required to treat this widespread disease. Gut hormones such as peptide YY (PYY) have emerged as candidate therapies for obesity which activate natural satiety pathways, reduce food intake and therefore body weight. We report the results from a Phase I trial of a PYY analogue, Y14, in overweight volunteers. Methods: In a first time in human Phase I randomized placebo-controlled trial, an extended-release formulation of Y14 with zinc chloride for subcutaneous injection, utilizing various Zn:peptide molar ratios, was tested. Part A of the trial was a partially blinded single ascending dose study. Part B was double-blinded and tested multiple ascending doses given at 7–14 day intervals over the course of 28 days with up to 5 doses given per subject. The primary outcome was the safety and tolerability of extended-release Y14; the secondary outcome was to assess its pharmacokinetics. Exploratory outcomes included the assessment of food consumption, body weight and glucose tolerance in response to 75g oral glucose load after multiple doses of Y14. [ClinicalTrials.gov NCT03673111]. Findings: Between Apr 11, 2017, and Dec 24, 2018 44 participants were enrolled into Part A of the trial and 24 into Part B and were included in the full analysis and safety datasets. The multiple doses of Y14 given in Part B led to significant mean placebo-subtracted reductions in body weight of 2.76 to 3.59 kg at 31 days after the first dose, in association with profound reductions in food intake and no evidence of tachyphylaxis. No significant changes in glucose tolerance were detected. The most common adverse events were nausea, vomiting and injection site reactions. No serious adverse events occurred. The pharmacokinetic characteristics of extended-release Y14 were compatible with administration every 7–14 days. Interpretation: Our results support the continued development of Y14 as a novel treatment for obesity. Funding: UK Medical Research Council Developmental Pathway Funding Scheme.

SUN-110 The Role Of RasD2 In Metabolism And Obesity

RasD2 encodes for a small GTP-binding protein that was initially identified and studied for its highly enriched expression in the striatum, where its expression is regulated by thyroid hormone and dopamine. Subsequently RasD2 has been shown to also be expressed in other tissues, including pancreatic islets, kidney, and heart. Microarray analysis comparing gene expression of islets from C57BL/6J mice fed a high-fat diet (HFD) vs regular chow found that RasD2 expression was increased in islets of mice fed a HFD, and RasD2 expression has been shown to increase in response to various insulin secretagogues, like imidazoline and sulfonylurea. However the downstream effects of these changes in RasD2 expression have never been fully elucidated. The aim of this project is to more fully characterize the role of RasD2 in metabolism. C57BL/6J mice with deletion of RasD2 were fed HFD (45% kcal fat) or regular chow and compared to their WT littermates. Glucose homeostasis was assessed with intraperitoneal glucose tolerance test and body composition was measured using 1H-Magnetic Resonance Spectroscopy. When fed a regular diet, RasD2 KO mice had slightly lower body weight, but had similar body composition and no significant change in glucose tolerance when compared to WT littermates. When fed HFD, RasD2 KO and WT mice both gained a similar amount of body weight and developed glucose intolerance, but KO mice had less fat, and a higher proportion of lean mass. Using QPCR and western blot, we showed that RasD2 is expressed in adipose tissue, and that RasD2 expression increases in 3T3-L1 cells during differentiate into adipocytes. These data suggest a role for RasD2 in regulates energy homeostasis and/or adipogenesis, which may prove to be an attractive target in the battle against obesity. Ongoing studies will elucidate a more detailed mechanism.

In vivoadministration of the C16:0 fatty acid isoform of sulfatide increases pancreatic sulfatide and enhances glucose-stimulated insulin secretion in Zucker fatty (fa/fa) rats

Sulfatide is present in the secretory granules of beta cells and has been shown, in vitro, to be involved in insulin processing and secretion. Of particular interest is one of the major sulfatide isoforms in the beta cells, the C16:0 fatty acid isoform, which has been shown to be involved in insulin crystal preservation in vitro. The aim of this study was to investigate the ability of C16:0 fatty acid isoform of sulfatide to affect insulin secretion and/or action and glycaemic control in the adipogenic 'prediabetic' Zucker rat. The C16:0 sulfatide was administered to Zucker rats for 10 weeks, and fasting levels of plasma insulin and glucose were measured as well as levels after an intravenous (i.v.) glucose load. In addition, the sulfatide expression, examined by thin-layer chromatography-enzyme-linked immunosorbent assay and mass spectrometry, in the pancreas of C16:0 sulfatide-treated Zucker rats was compared to controls. The in vivo treatment of Zucker rats with C16:0 sulfatide resulted in significantly elevated glucose-stimulated insulin secretion (60-80% increase, p < 0.05), without significant changes in glucose tolerance. The treatment was associated with an ameliorated first-phase insulin response (3-4-fold, p = 0.009, 0.016) and a 60% increase of pancreatic sulfatide content (p = 0.001), possible by an uptake of C16:0 sulfatide. The fasting hyperinsulinaemia and blood glucose levels were unchanged. The treatment with C16:0 sulfatide elevates glucose-stimulated insulin secretion and enhances sulfatide content in the pancreas of Zucker rats.

The effects of low-dose growth hormone in HIV-infected men with fat accumulation: a pilot study.

Pharmacologic doses of growth hormone (GH) reduce HIV-associated fat accumulation but may worsen glucose metabolism. We investigated the effects of a low dose of GH (1 mg per day) in HIV-infected men with fat accumulation and found that such treatment reduced total fat and increased lean body mass without significant changes in glucose tolerance or insulin sensitivity. Visceral adipose tissue (VAT) levels did not change significantly for the group as a whole, although a reduction in the VAT level was seen in patients with a greater VAT level at baseline.

The effects of felodipine and amlodipine on glucose and lipid metabolism in patients affected by non—insulin-dependent diabetes mellitus and hypertension: a comparative, randomized, parallel-group study

Fifty-three patients with non—insulin-dependent diabetes mellitus and hypertension were randomly treated with extended-release felodipine 10 mg/d, amlodipine 10 mg/d, or placebo for 6 weeks. Mean clinostatic systolic and diastolic blood pressures were significantly reduced from baseline with both drug treatments ( P < 0.0001), whereas placebo affected only systolic pressure. Neither felodipine nor amlodipine treatment led to any significant change in glucose tolerance (as measured by using the oral glucose tolerance test), C-peptide secretion, fructosamine, or glycated hemoglobin A 1c levels. Similarly, neither treatment appeared to increase triglyceride levels, total cholesterol levels, or its fractions. All safety parameters remained stable during the study. There was no significant trend in electrocardiogram (ECG) variations for any of the treatments, but one patient in the amlodipine group showed ECG signs compatible with acute myocardial infarction. These data suggest that in diabetic hypertensive patients, both felodipine and amlodipine have a neutral effect on glucose and lipid metabolism while retaining their hemodynamic efficacy. Therefore, their use as first-step antihypertensive therapies can be recommended in such patients.

Investigation of the mechanism(s) of 8‐OH‐DPAT‐mediated inhibition of plasma insulin in spontaneously hypertensive rats

1. Effects of the prototype selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-dipropylamino)tetralin (8-OH-DPAT), were studied on the glycaemia and insulinaemia in conscious spontaneously hypertensive (SH) rats concurrently with blood pressure (BP) and heart rate (HR); underlying mechanism(s) were investigated in anaesthetized and pithed SH rats and in the perfused rat pancreas. 2. Intravenous (i.v.) injections of 8-OH-DPAT (150 micrograms kg-1, i.v.) into fasted conscious but not anesthetized SH rats increased glycaemia; glucose-stimulated (i.v. glucose tolerance test) plasma insulin levels were significantly inhibited in both cases without significant changes in glucose tolerance. Metabolic changes were associated with prominent decreases in BP and HR. 3. No inhibitory effect of 8-OH-DPAT, 150 micrograms kg-1 i.v., on glucose-stimulated plasma insulin was observed in pithed SH rats; in contrast, clonidine (8 micrograms kg-1 i.v.), produced marked inhibition of insulin levels in association with glucose intolerance. Neither compound decreased BP; rather, pronounced vasopressor effects were observed. 4. In the isolated perfused pancreas of the rat, 8-OH-DPAT, at 10(-8) and 10(-7) M, concentrations known to activate 5-HT1A receptors in vitro, failed to modify glucose-stimulated insulin release. Inhibition (39 +/- 7%) was seen only at a high concentration of 10(-6) M. 5. The present data suggest that like the cardiovascular effects of 8-OH-DPAT, the inhibition of glucose-stimulated insulin release is mediated via the central nervous system. However, it is suggested that different mechanisms are involved in the cardiovascular actions and metabolic effects of 8-OH-DPAT in the SH rat; the latter are likely to reflect a consequence of activation of the hypothalamic-adrenal axis.

Indoramin in the Hypertensive Diabetic Patient

In 32 hypertensive diabetic patients a study was performed to determine the effects of indoramin on blood pressure and blood glucose, plasma insulin, C-peptide, serum total cholesterol, and triglyceride levels. All patients evaluated showed a significant fall in blood pressure with daily doses of 50 to 200 mg of indoramin. In six insulin-dependent diabetic patients there was no change in diabetic control and no effect on the incidence of hypoglycaemia. In 18 noninsulin-dependent diabetics monitored for 3 months and in 14 followed for 12 months, there was no significant change in glucose tolerance after a 75 g glucose dose; mean plasma C-peptide levels and 2 h insulin levels were increased at 12 months. Mean weight and mean fasting cholesterol and triglyceride concentrations were unchanged. Nine patients withdrew because of side effects, mainly drowsiness and lethargy.

Effect of acetylsalicylic acid on blood glucose and glucose regulatory hormones in mild diabetes

In order to investigate the effect of acetylsalicylic acid (ASA) on glucose tolerance and glucose regulatory hormones, ASA was given to 14 diabetic patients for seven days by two different methods. A 50 g oral glucose tolerance test (OGTT) was performed before and after the treatment. Nine of 14 diabetics received a dosage of 1.5 g of ASA three times a day for seven days plus 1.5 g on the eighth day one hr before the test (group I). The other 5 patients had the same dosage of ASA as group I, but were not administered ASA prior to the second OGTT (group II). In group I the ASA treatment improved the glucose tolerance associated with a sustained rise of plasma insulin significantly, whereas no significant change in glucose tolerance or plasma insulin was observed in group II compared the pretreatment level. The ASA had no significant effect on plasma glucagon or gastric inhibitory polypeptide in either group I or group II. These results suggest that ASA allievates glucose intolerance in maturity onset diabetics by a direct enhancement of insulin secretion, and, moreover, that it is important to maintain elevated ASA concentrations in their blood.

An incremental-dose combined oestrogen-progestogen oral contraceptive: effects on body weight, blood pressure, and biochemical parameters.

An evaluation is presented of the effects of an incremental-dose combined oestrogen-progestogen contraceptive (0.05 mg ethinyl oestradiol throughout the cycle plus d-norgestrel 0.05 mg for the first 11 days and 0.125 mg for the subsequent 10 days). The majority of women showed weight changes less than 1.0 kg; a weight gain in excess of 2 kg was observed in 11.4% and a similar loss in 14.3%. The net change in blood pressure after 12 months was a slight reduction; no excessive elevation of pressure was recorded. Although no significant change in glucose tolerance was noted, triglyceride levels became progressively elevated; the increase in cholesterol levels were observed mainly in the second half of the cycle. Changes occurred in some but not all haematologic parameters: a significant increase in plasminogen level and decrease in activated prothrombin time; factors 7, 9 and 10 were progressively increased, whereas factors 5, 8, fibrinogen and antithrombin activity remained unaltered. This new preparation provides effective contraception with satisfactory cycle control and body weight changes. It is particularly useful in women who require additional oestrogen.

Impairment of growth hormone and insulin secretion in hyperthyroidism.

Abstract. The pattern of growth hormone (GH) and im‐munoreactive insulin (IRI) secretion in response to insulin hypoglycaemia, arginine infusion and oral glucose load has been investigated in a group of hyperthyroid subjects. In twenty patients, compared with twenty normal controls, GH secretion was significantly reduced in response to both insulin hypoglycaemia and arginine infusion. Arginine‐induced IRI secretion was also clearly decreased. In ten patients who had undergone a 100 g oral glucose load, hyperglycaemia failed to suppress GH levels, which increased paradoxically. Slightly impoverished IRI secretion and impaired glucose tolerance were observed in these subjects. In five patients, re‐examined soon after restoration of euthyroidiszn, no significant changes in glucose tolerance and IRI secretion were noted; instead, a slightly improved GH response to the provocative stimuli and the restoration of a normal GH suppression by glucose were observed. – The possibility is emphasized that in hyperthyroidism an enhancement of the catecholamine effect induced by thyroid hormones is involved in the diminished GH and IRI secretion.

The effect of a 'sucrose-free' diet on oral glucose tolerance in man.

(1) 19 members of an Antarctic expedition were fed on a diet in which sucrose was replaced by glucose and calcium cyclamate for 14 weeks. Oral glucose tolerance tests were carried out whilst on this diet and for a comparable period of time when on the normal base diet. (2) Changes in body weight were small and not significant. (3) Although blood glucose levels were significantly lower 0.5 h after ingestion of the glucose load on the ‘sucrose-free’ diet towards the end of the diet period, compared with values obtained on the normal base diet, this change was reversed at 1 and 1.5 h after ingestion of the glucose load. (4) It is concluded that there is a small but significant change in glucose tolerance after nine weeks on a ‘sucrose-free’ diet.

Reversal of progesterone-enhanced insulin production by human chorionic somatommammotropin.

The interactions between human chorionic somatomammotropin (HCS) and progesterone in their effect on glucose and insulin metabolism were assessed in 10 female rhesus monkeys. Treatment with HCS alone (50 mg im twice daily for 7 days) produced decreased sensitivity to the hypoglycemic effect of exogenous insulin, but no significant change in glucose tolerance or the mean total serum insulin responses (ΣI40) to iv glucose (1 g⁄kg). By contrast, progesterone administration (5 mg daily in olive oil sc×3 weeks) led to significantly increased mean SI40 and mean initial rate of insulin release (Δl⁄ΔG10) in association with significantly slower mean glucose disappearance rate after iv glucose. Combined HCS-progesterone treatment blocked the augmented insulin responses (ΣI40 and Δl⁄ ΔG10) produced by progesterone alone, while glucose tolerance remained deteriorated. These results indicate that HCS affects carbohydrate metabolism through at least 2 mechanisms: a) by increasing peripheral resistance to insulin, and ...

Blood glucose levels and glucose tolerance in women with subclinical diabetes receiving an oral contraceptive

This study evaluated the effect of an ovulatory suppressive drug norethynodrel (2.5 mg) and mestranol (.1 mg enovid) used as an oral contraceptive on carbohydrate metabolism and in particular on the fasting blood sugar and intravenous glucose tolerance of young women with subclinical diabetes. 3 groups were studied 1) 12 nonobese women having subclinical diabetes mellitus not receiving insulin 2) 22 healthy nonobese women starting oral contraceptives and 3) 26 healthy nonobese women receiving no medication which was the control group. The mean value of the plasma glucose disappearance rate for Groups 1 and 2 had decreased significantly after 3 months therapy. No significant change in glucose tolerance had occurred with time in Group 3 (controls). It was suggested that glucose tolerance should be investigated and in those subjects who exhibit definite carbohydrate metabolic derangement oral contraceptive therapy should be avoided.

Improvement in Glucose Tolerance of Fasting Obese Patients Given Oral Potassium

Potassium therapy during a 2-week fast led to a significant improvement in glucose tolerance in six obese patients. This improvement was associated with earlier and greater plasma insulin responses than observed when no potassium was given. Fasting for 2 weeks without potassium produced no significant change in glucose tolerance. Fasting with potassium supplementation maintained normal potassium balance and produced a slight rise in total body potassium (K-40). When patients were fasted without potassium, a statistically significant negative potassium balance developed and the total body potassium fell significantly. No correlation between plasmafree fatty acid values and glucose tolerance was observed. Potassium depletion during fasting appears to play a significant ce:roles in the deterioration of glucose tolerance. It is suggested that potassium therapy increases the ability of the pancreas to secrete insulin in the presence of hyperglycemia.

Reproducibility of a glucose tolerance test.

A statistical method is described for testing the significance of changes in the glucose tolerance of experimental subjects in different conditions. Statistically significant changes in glucose tolerance from day to day were observed in seven normal men who underwent glucose tolerance tests on 3 successive days. No statistically significant changes in glucose tolerance were found on the 2nd day after a glucose tolerance test in further experiments using five normal men. Possible physiological mechanisms by which the performance of a glucose test could cause alterations in glucose tolerance are discussed. Submitted on December 19, 1960