Role In Glucose Control Research Articles

A Systematic Review Evaluating Cinnamon's Effects on Glucose Utilizing a Ranking System to Assess Bias and Study Quality.

In the context of diabetes, the use of cinnamon continues to be among the most popular supplements taken by patients for glucose control. To strategically evaluate the available literature comparing various cinnamon species and statistically significant glucose effects after ranking studies based on two tools to assess bias and overall study quality, to clarify cinnamon's role in glucose control. The authors performed a systematic search based upon PRISMA guidelines. The search was conducted utilizing PubMed, AMED, CINAHL, EMBASE, Cochrane, and Medline databases, with the final search performed in September 2022 with restrictions to human subjects and English language. Electronic searches were conducted utilizing the keywords "diabetes mellitus" combined with Cinnamomum zeylanicum/Cinnamomum cassia/Cinnamomum verum combined with blood glucose (BG). A second search utilized "cinnamomum zeylanicum/cinnamomum cassia/cinnamomum verum" combined with "blood glucose," and a final search utilized "diabetes mellitus" combined with "cinnamon." Data extraction and ranking of included studies utilizing the risk of bias 2 tool and modified Heyland Methodological Quality Scoring tool were performed independently by two review authors. These authors compared their results and reconciled any differences in scoring to generate a final ranking of studies. A third author was available for any discrepancies that could not be resolved but was not needed. Forty-five studies were included in the review and were scored for bias and quality. Overall 62% demonstrated statistical significance for positive effects in at least one parameter around BG control. Applying the ranking systems reduced the percentage closer to 50%. Safety was extremely well documented across studies with few adverse effects. Results are limited by heterogeneity of glucose parameters, leading to studies being ranked individually and not synthesized. Cinnamon supplementation likely has a modest positive effect on BG. Based upon the strong safety profile, utilization of this spice as an adjunct to pharmacologic therapy is reasonable.

Metformin in the prevention of colorectal cancer with diabetes mellitus

The purpose of the review is to present an analysis of current literature data on the prospects of using the oncoprotective effect of metformin in colorectal cancer. Metformin is a drug with a long history, it is a first-line drug for the treatment of type 2 diabetes mellitus (DM2), as well as the most commonly prescribed drug worldwide. Modern researches show that in addition to its role in glucose control, metformin can reduce the risk and mortality from some malignancies and improve the response of patients with DM2 to certain types of cancer treatment. Accumulated data indicate that metformin could be a candidate drug for drug prevention of colorectal cancer.

Suppression of Glucagon-Like Peptide-1 Release by Inhibition of Intestinal NLRP3 Inflammasome Activation in Asc-/- and Nlrp3-/- Mice.

The glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone secreted by intestinal enteroendocrine L-cells, which plays a crucial role in glucose control, regulation, and protection from different pathological conditions such as diabetes mellitus. The present study sought to test whether GLP-1 release increases gut injury with a high-fat diet (HFD) and whether this GLP-1 release is associated with NLRP3 inflammasome activation. Our results showed that the NLRP3 inflammasome is activated in the intestinal tissue of wild-type mice on a HFD, accompanied by GLP-1 overexpression. The number of intestinal L-cells and the GLP-1 level in serum are increased in WT mice with HFD. However, in the Asc–/– and Nlrp3–/– mice, these HFD-induced intestinal and serum GLP-1 changes were suppressed. Using confocal microscopy, the colocalization of GLP-1 and FLICA that labels activated caspase-1 in intestine was decreased in the Asc–/– and Nlrp3–/– mice compared to WT mice. Mechanistically, the inhibitor of caspase-1 or HMGB1 blocker is used to demonstrate the regulatory action of NRLP3 inflammasome in GLP-1 release. It was found that the level of GLP-1 and its colocalization with IL-1β were reduced by inhibition of the caspase-1 activity, but not altered by blockade of HMGB1 action. Our results suggest that NLRP3 inflammasome activation triggers GLP-1 production from the intestine, which is associated with IL-1β, but not with HMGB1. These findings for the first time provide evidence that the activation of NLRP3 inflammasome in the intestine increases GLP-1 release in mice, which may serve as an adaptive response to intestinal inflammation.

The incretin hormone GIP is upregulated in patients with atherosclerosis and stabilizes plaques in ApoE−/− mice by blocking monocyte/macrophage activation

ObjectiveThe incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by the gut after food intake leading to pancreatic insulin secretion and glucose lowering. Beyond its role in glucose control, GLP-1 was found in mice and men to beneficially modulate the process of atherosclerosis, which has been linked to improved cardiovascular outcome of patients with diabetes at high cardiovascular risk treated with GLP-1 receptor agonists. However, little is known on the role of the other main incretin in the cardiovascular system. The aim of this study was to characterize GIP in atherosclerotic cardiovascular disease. Methods and resultsSerum concentrations of GIP were assessed in 731 patients who presented for elective coronary angiography at the University Hospital Aachen. While GIP concentrations were not associated with coronary artery disease (CAD), we found 97 patients with PAD (peripheral artery disease) vs. 634 without PAD to have higher circulating GIP levels (413.0 ± 315.3 vs. 332.7 ± 292.5 pg/mL, p = 0.0165). GIP levels were independently related to PAD after multivariable adjustment for CAD, age, sex, BMI, hypertension, diabetes, CRP, WBC, and smoking. To investigate the functional relevance of elevated GIP levels in human atherosclerotic disease, we overexpressed GIP (1–42) in ApoE−/− mice fed a Western diet for 12 weeks using an adeno-associated viral vector system. GIP overexpression led to reduced atherosclerotic plaque macrophage infiltration and increased collagen content compared to control (LacZ) with no change in overall lesion size, suggesting improved plaque stability. Mechanistically, we found GIP treatment to reduce MCP-1-induced monocyte migration under In vitro conditions. Additionally, GIP prevented proinflammatory macrophage activation leading to reduced LPS-induced IL-6 secretion and inhibition of MMP-9 activity, which was attributable to GIP dependent inhibition of NfκB, JNK-, ERK, and p38 in endotoxin activated macrophages. ConclusionElevated concentrations of the incretin hormone GIP are found in patients with atherosclerotic cardiovascular disease, while GIP treatment attenuates atherosclerotic plaque inflammation in mice and abrogates inflammatory macrophage activation in vitro. These observations identified GIP as a counterregulatory vasoprotective peptide, which might open new therapeutic avenues for the treatment of patients with high cardiovascular risk.

Benefits of Nut Consumption on Insulin Resistance and Cardiovascular Risk Factors: Multiple Potential Mechanisms of Actions.

Epidemiological and clinical studies have indicated that nut consumption could be a healthy dietary strategy to prevent and treat type 2 diabetes (T2DM) and related cardiovascular disease (CVD). The objective of this review is to examine the potential mechanisms of action of nuts addressing effects on glycemic control, weight management, energy balance, appetite, gut microbiota modification, lipid metabolism, oxidative stress, inflammation, endothelial function and blood pressure with a focus on data from both animal and human studies. The favourable effects of nuts could be explained by the unique nutrient composition and bioactive compounds in nuts. Unsaturated fatty acids (monounsaturated fatty acids and polyunsaturated fatty acids) present in nuts may play a role in glucose control and appetite suppression. Fiber and polyphenols in nuts may also have an anti-diabetic effect by altering gut microbiota. Nuts lower serum cholesterol by reduced cholesterol absorption, inhibition of HMG-CoA reductase and increased bile acid production by stimulation of 7-α hydroxylase. Arginine and magnesium improve inflammation, oxidative stress, endothelial function and blood pressure. In conclusion, nuts contain compounds that favourably influence glucose homeostasis, weight control and vascular health. Further investigations are required to identify the most important mechanisms by which nuts decrease the risk of T2DM and CVD.

Insulin mimetic peptide S371 folds into a helical structure.

Insulin plays a crucial physiological role in glucose control by initiating a number of signaling events on binding and activating its cell surface receptor. Insulin mimics have, therefore, become promising agents for treating diabetes and to probe the mechanism of interaction of insulin with its receptor. Specifically, many insulin-mimetic peptide sequences have been discovered and found to selectively function as agonists and antagonists, but their structures and the mechanistic details of their interactions with the receptor remain challenging to characterize. In this work, we have studied the folding properties and structure of a Site 1 insulin mimetic peptide S371 that has sequence similarities with the insulin B-chain as well as with a critical hormone-binding element of the receptor known as the C-terminal (CT) peptide. We first validated our simulation approaches by predicting the known solution structure of the insulin B-chain helix and then applied them to study the folding of the mimetic peptide S371. Our data predict a helical fold for the first 16 residues of S371 that has a resemblance to the helical motifs in the insulin B-chain and CT. We also propose receptor-bound models of S371 that provide mechanistic explanations for competing binding properties of S371 and CT to the Site 1 of IR. © 2017 Wiley Periodicals, Inc.

Spatiotemporal Modeling of Triggering and Amplifying Pathways in GLP-1 Secreting Intestinal L Cells

Glucagon-like peptide 1 (GLP-1) is secreted by intestinal L-cells, and augments glucose-induced insulin secretion, thus playing an important role in glucose control. The stimulus-secretion pathway in L-cells is still incompletely understood and a topic of debate. It is known that GLP-1 secreting cells can sense glucose to promote electrical activity either by the electrogenic sodium-glucose cotransporter SGLT1, or by closure of ATP-sensitive potassium channels after glucose metabolism. Glucose also has an effect on GLP-1 secretion downstream of electrical activity. An important aspect to take into account is the spatial organization of the cell. Indeed, the glucose transporter GLUT2 is located at the basolateral, vascular side, while SGLT1 is exposed to luminal glucose at the apical side of the cell, suggesting that the two types of transporters play different roles in glucose sensing. Here, we extend our recent model of electrical activity in primary L-cells to include spatiotemporal glucose and Ca2+ dynamics, and GLP-1 secretion. The model confirmed that glucose transportation into the cell through SGLT1 cotransporters can induce Ca2+ influx and release of GLP-1 as a result of electrical activity, while glucose metabolism alone is insufficient to depolarize the cell and evoke GLP-1 secretion in the model, suggesting a crucial role for SGLT1 in triggering GLP-1 release in agreement with experimental studies. We suggest a secondary, but participating, role of GLUT2 and glucose metabolism for GLP-1 secretion via an amplifying pathway that increases the secretion rate at a given Ca2+ level.

Bariatric surgery and obesity: influence on the incretins.

The gut hormone incretins have an important physiological role in meal-related insulin release and post-prandial glucose control. In addition to weight loss, the incretin hormones have a role in glucose control after bariatric surgery. The release of incretins, and specifically of glucagon-like peptide (GLP)-1, in response to the ingestion of nutrients, is greatly enhanced after gastric bypass (RYGBP). The rapid transit of food from the gastric pouch to the distal ileum is responsible for the greater GLP-1 release after RYGBP. The incretin effect on insulin secretion, or the greater insulin response to oral glucose compared to an isoglycemic intravenous glucose challenge, is severely impaired in patients with type 2 diabetes, but is recovered rapidly after RYGBP. The improvement in insulin secretion rate and β-cell sensitivity to oral glucose after RYGBP is mediated by endogenous GLP-1, and is abolished by exendin 9-39, a specific GLP-1 receptor antagonist. While calorie restriction and weight loss have major effects on the rapid and sustained improvement of fasted glucose metabolism, the enhanced incretin effect is a key player in post-prandial glucose control after RYGBP.

Progressive decrease of proinsulin secretion in sulphonylurea-treated type 2 diabetes

Progressive deterioration of β-cell function is proposed as a disease-related factor of sulphonylurea (SU) failure in type 2 diabetes. If it gradually worsens over time then disease duration may mirror the progressive β-cell deterioration. The aim of the present study is to assess whether or not disease duration is influential in remodelling the secretion pattern of insulin-like molecules and in glucose control of SU-treated type 2 diabetes. A research model is used to investigate proinsulin secreting capacity over time, using two groups of patients: i) disease duration <5 years (n= 62), comprising SU responders (SUr; n=48) and SU failures (SUf; n=14); and ii) disease duration ≥ 5 years (n= 37), comprising an SUr group (n=17) and an SUf group (n=20). Blood samples are taken at 0 h, 0.5 h 1 h, 2 h and 3 h during a standard oral glucose tolerance test and measured for glucose, total proinsulin (TPI), intact proinsulin (IPI) and specific insulin (SI) concentrations. Pairwise comparison of estimated marginal means of blood glucose, SI, IPI and TPI levels at each time point are carried out between groups and subgroups. (SUr vs. SUf). Homa insulin resistance index (IR index) is applied to analyse IR between the groups. It was found that patients with shorter disease duration had higher proinsulin (TPI and IPI) levels at all time points (P<0.05), together with a lower glucose level at 2 h and 3 h (P<0.05). Homa insulin index analysis showed no difference between the two groups (P=0.26). Results also showed that the SUr group had a significantly lower glucose level at 0h and 3h (P<0.05), although no significant difference in insulin and proinsulin levels was found between the SUr and SUf groups. In conclusion, proinsulin may play an important role in glucose control in SU-treated type 2 diabetes, but the effect is reduced in SUf patients.

The impact of GAL6, GAL80, and MIG1 on glucose control of the GAL system in Saccharomyces cerevisiae.

The role of the proteins encoded by the GAL80 gene, the MIG1 gene and the GAL6 gene in glucose control of galactose consumption by Saccharomyces cerevisiae was studied by physiological characterisation of various GAL mutant strains. Dynamic experiments with the CEN.PK 113-7D wild-type strain and a deltagal80deltamig1 double-mutant strain in aerobic nitrogen-limited continuous cultivations at a dilution rate of 0.1 h(-1), showed simultaneous glucose and galactose consumption by the deltagal80deltamig1 strain. The wild-type strain did not consume galactose in the presence of glucose. Aerobic batch cultivations on glucose-galactose mixtures with the wild-type strain and with recombinant strains with a de-regulated GAL system (the deltagal80deltamig1 strain, a deltagal6 deleted strain, a deltagal6deltagal80deltamig1 triple mutant, and a deltagal6deltagal80deltamig1 triple mutant harbouring a GAL4 high-copy vector) were carried out. Generally, a reduction of glucose control lowered the maximum specific growth rate on glucose and increased the ethanol yield obtained on galactose with more than 100%. In contrast to the wild-type strain, the deltagal6deltagal80deltamig1 triple mutant strain consumed glucose and galactose simultaneously, and this strain also showed the highest ethanol production with an overall ethanol yield of 0.35 g g-1 sugar, which is 17% higher than the yield on glucose obtained with the wild-type strain. GAL80 and MIG1 were demonstrated to be responsible for the majority of the glucose control on the GAL system, whereas GAL6 has a minor role in glucose control. Deletion of GAL6 was shown to have a major impact on biomass and ethanol formation when cells were grown on galactose, and from the data obtained we speculate that Gal6 may be involved in mRNA degradation of the GAL gene transcripts.

Investigation of the impact of MIG1 and MIG2 on the physiology of Saccharomyces cerevisiae

The gene functions of MIG1 and MIG2 are well known for their role in glucose control in Saccharomyces cerevisiae. A prototrophic mig1 disruptant (T468) and mig1 mig2 double disruptant (T475) as well as their congenic wild-type strain (CEN.PK 113-7D) were analysed for changes in their peripheral metabolism (batch cultivations on sugar mixtures) and central metabolism (batch and continuous cultivations as well as acceleratostats). Sucrose metabolism was alleviated of glucose control in the mig1 disruptant, and even more so in the mig1 mig2 disruptant compared with their wild-type strain. The lag phase in a batch cultivation grown on a glucose–galactose mixture was reduced by 50% in either disruptant, i.e. additional disruption of MIG2 in a mig1 background did not further alleviate galactose metabolism from glucose control. In contrast, both disruptants exhibited a more stringent glucose control of maltose metabolism compared with the wild-type strain. Growing on glucose, the mig1 mig2 double disruptant exhibited a 12% higher specific growth rate than the wild-type strain, as well as a significantly higher respiratory capacity.