Postprandial Serum Insulin Levels Research Articles

Nicotinamide mononucleotide (NMN) intake increases plasma NMN and insulin levels in healthy subjects

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme of the NAD+-dependent protein deacetylase sirtuin-1 (SIRT1). An increase in NAD+ concentration induces SIRT1 activation that results in various health benefits. Since nicotinamide mononucleotide (NMN) is a precursor of NAD+, NMN ingestion is expected to have multiple health benefits such as alleviation of aging, lifestyle-related and neurodegenerative diseases, through the activation of SIRT1. In this study, we aimed to determine the effects of daily NMN ingestion on plasma levels of NMN and NAD+. Healthy volunteers received 250mg of NMN once a day in the morning (n=11) for 12 weeks, and the plasma concentrations of NMN and NAD+ were measured monthly. Physiological and laboratory tests were performed within 2h after lunch (at 2 pm) before and during NMN administration. Oral administration of NMN increased the plasma concentrations of NMN and NAD+, and the postprandial serum insulin levels. The elevation levels of NMN and insulin varied widely among individuals. No adverse symptoms were observed in the participants. Oral administration of NMN elevates plasma levels of NMN and NAD+, and postprandial serum insulin levels.

Antidiabetic effect of withanolides and liraglutide on serum insulin level and pancreatic histology in diabetic rats.

Objectives: Type 2 diabetes is characterized by hyperglycemia and occurs as a result of insulin resistance and pancreatic beta cells failure to compensate. Present study was conducted to determine the antidiabetic effect of Withania coagulans and liraglutide on postprandial serum insulin levels and pancreatic histological features in streptozotocin induced diabetic rat. Study Design: This Randomized Control Trial. Setting: At multidisciplinary lab Islamic International Medical College, Rawalpindi in collaboration with Animal House, National Institute of Health, Islamabad. Period: From March 2016 to April 2017. Material and Methods: Forty male Sprague daily rats were randomly divided into normal Control Group A (n=10) and Experimental Group (n=30). Experimental group was given streptozotocin (30mg/kg/day) intraperitoneally for 5 days and diabetes was confirmed in experimental group by measuring fasting blood glucose level (mg/dl). Experimental group was divided further into Group B (Diabetic control), Group C (Withania coagulans treated) and Group D (Liraglutide treated). Group C were given Withania coagulans in addition to normal diet and Group D received Liraglutide besides normal diet for 30 days. Second sampling for evaluating postprandial serum insulin level and pancreatic histology was done after 30 days. Result: Postprandial serum insulin levels of Withania coagulans treated Group C (5.54 + 0.23 μU/ml) and Liraglutide treated Group D (6.06 + 0.17 μU/ml) were significantly raised in comparison with Diabetic control Group B (3.50 + 0.19 μU/ml), whereas islets of Langerhans cell morphology were markedly improved in Group C and D as compared to Group B. Conclusion: Withania coagulans significantly increases postprandial serum insulin level and improves pancreatic beta cells architecture.

Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet-induced obesity rats.

Long‐term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90 days. The study was performed using two different diet‐induced obesity (DIO) rat models: one using a high‐fat diet (HFD) and the other using a high‐carbohydrate diet (HCHD). Autologous SAT transplant reduced hypertrophic adipocytes, improved insulin sensitivity, reduced hepatic lipid content, and fasting serum‐free fatty acids (FFAs) concentrations in the two DIO models. In addition, the reductions in FFAs and glycerol were accompanied by a greater reduction in lipolysis, assessed via the phosphorylation status of HSL, in the transplanted adipose tissue localized in the omentum compared with that localized in the retroperitoneal compartment. Therefore, the improvement in hepatic lipid content after autologous SAT transplant may be partially attributed to a reduction in lipolysis in the transplanted adipose tissue in the omentum due to the direct drainage of FFAs into the liver. The HCHD resulted in elevated fasting and postprandial serum insulin levels, which were dramatically reduced by the autologous SAT transplant. In conclusion, the specific intraabdominal localization of the autologous SAT transplant improved the carbohydrate and lipid metabolism of adipose tissue in obese rats and selectively corrected the metabolic parameters that are dependent on the type of diet used to generate the DIO model.

Effects of miglitol, sitagliptin, and initial combination therapy with both on plasma incretin responses to a mixed meal and visceral fat in over-weight Japanese patients with type 2 diabetes. “The MASTER randomized, controlled trial”

To assess changes in circulating incretin levels and body fat compositions with initial combination therapy with α-glucosidase inhibitor and dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes (T2D). In this multicenter open-label 24-week trial, Japanese over-weight (BMI ≥ 25 kg/m(2)) patients with T2D not taking medication or taking metformin and/or sulfonylurea were randomly assigned to receive either 50mg of miglitol three times a day (M, n=14), 50mg of sitagliptin once a day (S, n=14), or a combination of both (M+S, n=13). Changes in plasma incretin levels during a meal tolerance test (MTT) and body fat composition with impedance method were evaluated. During MTT, postprandial plasma glucose levels decreased more after M+S than after M or S, and postprandial serum insulin levels decreased significantly after M and M+S whereas they increased after S. After M, active gastric inhibitory polypeptide (aGIP) decreased significantly at 30 min despite a significant increase at 120 min. After S, aGIP levels increased significantly throughout the MTT. After M+S, aGIP increased significantly at 0 and 120 min despite of significant decrease at 30 min. M+S further enhanced postprandial active glucagon-like peptide-1 levels during MTT than S did. Total body fat mass decreased significantly after M and M+S. Visceral fat mass decreased significantly only after M+S. Serum adiponectin increased significantly only after M+S. In over-weight patients with T2D, M+S may have a beneficial effect on adiposity with relation to these different effects on two incretins.

The insulinogenic effect of whey protein is partially mediated by a direct effect of amino acids and GIP on β-cells.

BackgroundWhey protein increases postprandial serum insulin levels. This has been associated with increased serum levels of leucine, isoleucine, valine, lysine, threonine and the incretin hormone glucose-dependent insulinotropic polypeptide (GIP). We have examined the effects of these putative mediators of whey’s action on insulin secretion from isolated mouse Langerhans islets.MethodsMouse pancreatic islets were incubated with serum drawn from healthy individuals after ingestion of carbohydrate equivalent meals of whey protein (whey serum), or white wheat bread (control serum). In addition the effect of individual amino acid combinations on insulin secretion was also tested. Furthermore, the stimulatory effects of whey serum on insulin secretion was tested in vitro in the absence and presence of a GIP receptor antagonist ((Pro(3))GIP[mPEG]).ResultsPostprandial amino acids, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) responses were higher after whey compared to white wheat bread. A stimulatory effect on insulin release from isolated islets was observed with serum after whey obtained at 15 min (+87%, P < 0.05) and 30 min (+139%, P < 0.05) postprandially, compared with control serum. The combination of isoleucine, leucine, valine, lysine and threonine exerted strong stimulatory effect on insulin secretion (+270%, P < 0.05), which was further augmented by GIP (+558% compared to that produced by glucose, P < 0.05). The stimulatory action of whey on insulin secretion was reduced by the GIP-receptor antagonist (Pro(3))GIP[mPEG]) at both 15 and 30 min (−56% and −59%, P < 0.05).ConclusionsCompared with white wheat bread meal, whey causes an increase of postprandial insulin, plasma amino acids, GIP and GLP-1 responses. The in vitro data suggest that whey protein exerts its insulinogenic effect by preferential elevation of the plasma concentrations of certain amino acids, GIP and GLP-1.

Consumption of dehydrated Opuntia ficus Indica (nopal) prevents the development of fatty liver by modifying hepatic lipid metabolism in obese Zucker fa/fa rats

Opuntia ficus indica (nopal), a plant rich in bioactive compounds, has been widely used in the traditional Mexican medicine to treat diabetes. Therefore in the present study, we investigated the effect of nopal consumption in the prevention of fatty liver in obese Zucker rats.Six weeks old male Zucker (fa/fa) rats (n=12 per group) were fed with a control diet (AIN‐93G; C) or C+ Nopal for 7 weeks. After 7 weeks of dietary treatment, rats fed C+nopal decreased by 50% hepatic triglycerides with respect to control and reduced hepatomegaly and macrovesicular steatosis. In addition, increased serum levels of adiponectin, mRNA expression of genes involved in lipid oxidation (PPARα, CPT1 and ACOX) and lipid export (MTTP and PLTP), hepatic CPT1 and MTTP protein levels. Furthermore, rats fed C+nopal decreased postprandial serum insulin levels; increased liver pAkt/Akt ratio in the postprandial state and significantly decreased serum ALT and AST levels.This study shows that nopal consumption prevents the development of fatty liver in obese Zucker rats by increasing fatty acid oxidation and VLDL synthesis,, improving liver insulin signaling. Supported by Grupo Produce DF 2010 (to NT)Grant Funding Source: Produce

Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects

BackgroundPrevious animal studies have shown that Curcuma (C.) longa lowers plasma glucose. C. longa may thus be a promising ingredient in functional foods aimed at preventing type 2 diabetes. The purpose of the study is to study the effect of C. longa on postprandial plasma glucose, insulin levels and glycemic index (GI) in healthy subjects.MethodsFourteen healthy subjects were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with capsules containing a placebo or C. longa. Finger-prick capillary and venous blood samples were collected before, and 15, 30, 45, 60, 90, and 120 min after the start of the OGTT to measure the glucose and insulin levels, respectively.ResultsThe ingestion of 6 g C. longa had no significant effect on the glucose response. The change in insulin was significantly higher 30 min (P = 0.03) and 60 min (P = 0.041) after the OGTT including C. longa. The insulin AUCs were also significantly higher after the ingestion of C. longa, 15 (P = 0.048), 30 (P = 0.035), 90 (P = 0.03), and 120 (P = 0.02) minutes after the OGTT.ConclusionsThe ingestion of 6 g C. longa increased postprandial serum insulin levels, but did not seem to affect plasma glucose levels or GI, in healthy subjects. The results indicate that C. longa may have an effect on insulin secretion.Trial registration numberNCT01029327

The Effects of Pistachios on Postprandial Glucose and Insulin Levels, Gut Satiety Hormones and Measures of Oxidative Stress

Background: Nuts are associated with a reduced risk of CHD and Type 2 Diabetes possibly relating to their favorable fat, protein and antioxidant profiles. Moreover, nuts have also been shown to reduce serum LDL‐C. Previous studies have demonstrated that pistachios decreased the postprandial glycemic response of white bread in a dose‐dependent manner and attenuated the glucose excursions of common carbohydrate foods when consumed with 2oz of pistachios.Objective: To assess the effect of pistachios on postprandial serum insulin levels, gut satiety hormone responses and measures of tissue oxidative stress.Methods: After an overnight fast, 15 healthy subjects consumed 2 iso‐caloric test meals and 1 control meal in a randomized fashion, each separated by 1 week. Test meals, with similar macronutrient profiles, consisted of white bread (97g) plus 2oz of pistachios; white bread (97g) plus butter (14g) and cheese (68g). The control meal was white bread. Capillary finger‐prick and venous blood samples were taken and subjective satiety measures via a visual analogue scale were assessed over 3 hours. The relative glycemic and insulinemic responses were assessed by calculating the incremental area under the 3h curve (IAUC).Results: Differences are assessed by least squares means with a Tukey adjustment for multiple comparisons. To be presented.Funding Support: Western Pistachio Association

Dominant-Negative Effects of a Novel Mutated Ins2 Allele Causes Early-Onset Diabetes and Severe β-Cell Loss in Munich Ins2C95S Mutant Mice

The novel diabetic mouse model Munich Ins2(C95S) was discovered within the Munich N-ethyl-N-nitrosourea mouse mutagenesis screen. These mice exhibit a T-->A transversion in the insulin 2 (Ins2) gene at nucleotide position 1903 in exon 3, which leads to the amino acid exchange C95S and loss of the A6-A11 intrachain disulfide bond. From 1 month of age onwards, blood glucose levels of heterozygous Munich Ins2(C95S) mutant mice were significantly increased compared with controls. The fasted and postprandial serum insulin levels of the heterozygous mutants were indistinguishable from those of wild-type littermates. However, serum insulin levels after glucose challenge, pancreatic insulin content, and homeostasis model assessment (HOMA) beta-cell indices of heterozygous mutants were significantly lower than those of wild-type littermates. The initial blood glucose decrease during an insulin tolerance test was lower and HOMA insulin resistance indices were significantly higher in mutant mice, indicating the development of insulin resistance in mutant mice. The total islet volume, the volume density of beta-cells in the islets, and the total beta-cell volume of heterozygous male mutants was significantly reduced compared with wild-type mice. Electron microscopy of the beta-cells of male mutants showed virtually no secretory insulin granules, the endoplasmic reticulum was severely enlarged, and mitochondria appeared swollen. Thus, Munich Ins2(C95S) mutant mice are considered a valuable model to study the mechanisms of beta-cell dysfunction and death during the development of diabetes.

Acarbose and metabolic control in patients with type 2 diabetes with newly initiated insulin therapy

This study was designed to investigate the effect of acarbose in patients with type 2 diabetes with newly initiated insulin treatment who had previously been insufficiently controlled with oral antihyperglycaemic agents [haemoglobin A(1c) (HbA(1c)) >/= 8%]. In this 20-week double-blind, placebo-controlled study, 163 patients were randomized to receive acarbose up to 100 mg three times a day or matching placebo. Both the groups were newly initiated with insulin, which was adjusted according to blood glucose values. Primary efficacy parameter was the change in HbA(1c) from baseline; changes in daily insulin doses were also assessed. Mean HbA(1c) was significantly reduced by acarbose compared with placebo (2.31 vs. 1.81%, p = 0.033). Insulin doses were comparable at the end of the study. There was no difference in blood glucose and triglyceride levels between the treatment groups. Postprandial serum insulin levels increased in both treatment arms owing to insulin administration but less so under acarbose. In contrast to the placebo group, an increase in body mass index was prevented for acarbose-treated patients. As adjunct administration to newly initiated insulin therapy, acarbose enhances the optimization of blood glucose control in patients with type 2 diabetes.

Phenotypic Heterogeneity in Body Fat Distribution in Patients with Atypical Werner’s Syndrome Due to Heterozygous Arg133Leu Lamin A/C Mutation

A heterozygous missense mutation substituting arginine at position 133 to leucine in the lamin A/C protein has been reported in two young women with clinical features of short stature, bird-like faces, and early onset of aging processes. The objective of the study was to carry out detailed phenotyping of these two women by evaluating the pattern of fat loss using anthropometry, dual-energy x-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI) and study metabolic abnormalities in glucose and lipid metabolism. The study consisted of descriptive case reports. The study was conducted at a referral center. Patient 1 was a 23-yr-old African-American female with progeroid features. Patient 2 was a 24-yr-old Caucasian female with generalized lipodystrophy, hypertriglyceridemia, and severe insulin resistance diabetes who required more than 200 U of insulin daily. There were no interventions. Body fat distribution to characterize pattern of lipodystrophy and nuclear morphology abnormalities in skin fibroblasts were studied. Patient 1 had normal body fat (27%) by DEXA. However, MRI revealed relative paucity of sc fat in the distal extremities, with preservation of sc truncal fat. She had impaired glucose tolerance and elevated postprandial serum insulin levels. Patient 2, in contrast, had only 11.6% body fat as determined by DEXA and had generalized loss of sc and intraabdominal fat on MRI. Skin fibroblasts from patient 2 showed marked abnormal nuclear morphology, compared with those from patient 1. Despite the deranged nuclear morphology, the lamin A/C remained localized to the nuclear envelope, and the nuclear DNA remained within the nucleus. Atypical Werner's syndrome associated with Arg133Leu mutation in the LMNA gene presents with a phenotypically heterogeneous disorder. Furthermore, the severity of metabolic complications seems to correlate with the extent of lipodystrophy.

Miglitol: a review of its therapeutic potential in type 2 diabetes mellitus.

Miglitol, the first pseudomonosaccharide alpha-glucosidase inhibitor, smooths postprandial peak plasma glucose levels and thus improves glycaemic control, which is reflected in a reduced glycosylated haemoglobin (HbA1c) level. This oral antihyperglycaemic agent is indicated for the treatment of patients with type 2 diabetes mellitus. Miglitol is generally well tolerated and, unlike the sulphonylurea agents, is not associated with bodyweight gain or hypoglycaemia when administered as monotherapy. The drug is systemically absorbed but is not metabolised and is rapidly excreted via the kidneys. Clinical trials with miglitol (usually 50 or 100 mg 3 times daily) in patients with type 2 diabetes mellitus consistently demonstrated a significant improvement in glycaemic control for periods of 6 to 12 months. There were also marked reductions in postprandial serum insulin levels, although miglitol generally had no effect on fasting insulin levels. In comparative studies miglitol had similar efficacy to acarbose, but at lower therapeutic doses (50 and 100 mg 3 times daily, respectively). In addition, although sulphonylurea agents provided superior reductions in HbA1c levels, miglitol provided similar or superior reductions in fasting and postprandial plasma glucose levels. In combination with other oral antidiabetic agents or insulin, miglitol improved glycaemic control in patients in whom metabolic control was suboptimal despite dietary and pharmacological intervention. Most adverse events associated with miglitol treatment involve disturbances of the gastrointestinal tract (most common effects are flatulence, abdominal pain and diarrhoea). These symptoms are usually dose dependent, mild to moderate in severity, occur at the onset of treatment, decline with time and resolve promptly on discontinuation of the drug or with dosage adjustment. As monotherapy, miglitol is not associated with hypoglycaemia, but concomitant use with other oral antidiabetic agents may necessitate dosage adjustment of the other agents. Miglitol had no significant effects on renal, cardiovascular, respiratory or haematological parameters in long term studies. No dosage adjustments are required in elderly patients, in those with hepatic impairment or in those with mild to moderate renal insufficiency. In long term, well designed trials miglitol reduces fasting and postprandial plasma glucose levels, thus improving glycaemic control, which is reflected in a reduced HbA1c level in patients with type 2 diabetes mellitus. Most adverse events associated with miglitol involve disturbances of the gastrointestinal tract. This agent is a useful first-line therapy in patients with type 2 diabetes mellitus insufficiently controlled by diet alone and as second-line or as adjuvant therapy in those insufficiently controlled with diet and sulphonylurea agents. Miglitol may prove particularly beneficial in elderly patients and those with hepatic impairment or mild to moderate renal impairment, in whom other oral antidiabetic agents are contraindicated or need to be used with caution.

Comparison of Acarbose and Gliclazide as First-line Agents in Patients with Type 2 Diabetes

SummaryAim: To compare the effect of acarbose and gliclazide on clinical findings, biochemical parameters and safety in type 2 diabetic patients insufficiently controlled with medical nutrition therapy (MNT).Methods: Seventy-two patients (age 35–70 years, BMI ≤ 35 kg/m2), who had not taken any oral antidiabetic drug previously, were randomised into two groups after a four-week placebo period, and treated for 24 weeks with acarbose (100 mg two to three times daily) and gliclazide (40–80 mg twice daily). The study was open and 57 patients (33 males and 24 females) completed it. MNT was provided for each patient based on personal requirements as defined by a dietitian. The effect of treatment was evaluated by fasting and postprandial (PP) metabolic parameters (blood glucose, insulin and C peptide levels), HbA1C and plasma lipid levels. In addition, side-effects were recorded and clinical examinations performed.Results: Both drugs were effective in reducing of HbA1C, fasting and PP blood glucose levels. However, PP serum insulin levels in the gliclazide group increased more than those in the group treated with acarbose (p = 0.007). Moreover, a small weight reduction was obtained with acarbose treatment but not with gliclazide. Lipid levels were favourably affected by both drugs. Total cholesterol levels decreased in both groups, the decrease only reaching significance in the acarbose group (p = 0.013). However, serum levels of LDL cholesterol decreased in both groups (acarbose and gliclazide, p = 0.033 and p = 0.023, respectively), but the ratio of HDL to LDL cholesterol increased in the acarbose group only (p = 0.045). Both treatments were generally well tolerated. Common complaints in the acarbose group were flatulence and meteorism (29.6%). However, 10.0% of the patients in the gliclazide group reported at least one mild hypoglycaemic episode.Conclusions: The results of the study demonstrate that acarbose and gliclazide were reasonably effective in improving metabolic control in patients insufficiently controlled with diet alone, and both treatments were well tolerated. Because of its effects on weight reduction and PP hyperinsulinaemia, acarbose may be preferred as a firstline drug, particularly in the treatment of overweight type 2 diabetic patients.

Large variations of sucrose in constant carbohydrate diets in type II diabetes

Several studies show that sucrose does not aggravate hyperglycemia in type II diabetes mellitus, but sucrose is still restricted in dietary recommendations. Since sucrose in high carbohydrate diets elevates fasting triglyceride levels, the effects of sucrose were evaluated in diets with fixed carbohydrate levels. Eighteen diabetic volunteers receiving no medication were given weight maintenance diets with 50 percent carbohydrate, 35 percent fat, 15 percent protein, and 120 g of sucrose for 10 days as inpatients. They were then randomly assigned diets of similar composition with either 220 g of sucrose (high sucrose diet) or less than 3 g of sucrose daily (complex carbohydrate [CHO] diet) for one additional month. There were no differences in fasting, one-, two-, and three-hour post-lunch serum glucose levels; 24-hour glycosuria; glycohemoglobin levels; fasting and postprandial serum triglyceride levels, or fasting high-density lipoprotein-cholesterol levels. Twelve patients with preexisting higher triglyceridemia had similar trends, but the postprandial triglyceride levels were lower in the high sucrose diet group of this subset (p <0.05 in the third week). Postprandial serum insulin levels declined in the second week on the complex CHO diet. More than 75-fold difference in sucrose intake with constant carbohydrate and fat did not affect glycemic or triglyceridemic control in type II diabetic patients. The reported high sucrosecarbohydrate-induced rise in fasting triglyceridemia was not present when a diet high in sucrose was given without changing total carbohydrate.

The Effect of Glibenclamide on Insulin Receptors in Normal Man: Comparative Studies of Insulin Binding to Monocytes and Erythrocytes*

In vivo studies in noninsulin-dependent diabetic patients have indicated that sulphonylurea drugs have an extra-pancreatic effect. To further elucidate the mechanisms of this action, we studied the effect of glibenclamide on in vivo and in vitro cellular insulin receptor binding in normal subjects. Oral administration of glibenclamide in dose of 2.5 mg/day increased insulin binding to monocytes by 70% (P less than 0.001), in spite of increased postprandial serum insulin levels. This change in insulin receptor binding occurred in the absence of changes in diet or body weight. In contrast, glibenclamide had no stimulatory effect on in vivo insulin binding to erythrocytes. The in vitro studies with monocytes revealed a dose-related insulin receptor stimulatory effect of glibenclamide (P less than 0.05), with a maximal effect of 20% above basal level. These data indicate that glibenclamide increases the insulin-binding ability of monocytes but not of erythrocytes. As the monocyte is judged a better model for studying insulin receptors on target cells than the erythrocyte, this effect may be responsible, at least in part, for the extrapancreatic effect of sulphonylureas, which seem to be of major importance for their hypoglycemic effect in noninsulin-dependent diabetic patients.

Effect of Low Sugar Intake upon Blood Lipids and Insulin Levels of Hyperlipemic Subjects

SummaryThe intake of simple sugars of 6 moderately hypertriglyceridemic, hypercholesterolemic subjects was reduced for 60 days. This restriction led to a moderate weight loss, a normalization of their previously elevated pre-beta lipoprotein levels and a moderate decrease in their pre- and postprandial hypertriglyceridemia. The elevated serum cholesterol and pre- and postprandial serum insulin levels were not normalized by the dietary change.