Glucose Homeostasis

Coenzyme Q10 is one of the most popular nutritional supplements, which has been discovered
in 1955. It is also known as ubiquinone, Q10, CoQ and vitamin Q10. This coenzyme has two
isoforms; the oxidized form, ubiquinone, is an electron carrier in mitochondrial respiratory
chain and the reduced form, ubiquinol, acts as an antioxidant.1,2 Studies reported its beneficial
effects in some diseases such as diabetes, heart failure, hypertension, and Parkinson disease.3,4
Q10 has also been proposed to be helpful in prevention and treatment of neurodegenerative
and mitochondrial related diseases.5
Q10 could potentially be effective on metabolic disorders
including lipid profile, blood pressure, glycemic control and insulin resistance in different diseases.

Benzylamine, a substrate of semicarbazide-sensitive amine ox-idase (SSAO), stimulates glucose transport in rat adipocytes and improves glucose disposal in diabetic rats only in the presence of vanadate. These effects have been described to result from a synergism between the hydrogen peroxide formed during amine oxidation and vanadate, via the generation of pervanadate, a powerful insulin mimicker. However, it has also been reported that benzylamine alone can stimulate glucose uptake and inhibit lipolysis in human fat cells. In this work, we therefore investigated whether benzylamine on its own was able to induce both in vivo and in vitro insulin-like responses in animal models other than rat. In rabbits, the i.v. infusion of 7 mol/kg benzylamine before a glucose tolerance test resulted in a net reduction of the hyperglycemic response without a change in insulin secretion. Benzylamine also improved glucose tolerance and reduced lipid mobilization in hyperglyce-mic/obese mice. In vitro, 0.1 mM benzylamine stimulated glucose transport and inhibited lipolysis in mouse and rabbit adipocytes. These effects were blocked by previous treatments with semicarbazide, a SSAO inhibitor. Levels of benzylamine oxidation were more elevated in mouse than in rabbit adipose tissues, whereas the reverse was observed for skeletal muscles. Finally, benzylamine was unable to stimulate insulin secretion by isolated pancreatic islets from both species and SSAO activity was hardly detectable in pancreas. Together, our results bring evidence that benzylamine on its own can improve glucose tolerance in rabbit and mouse, likely by stimulating glucose uptake via amine oxidase activation in insulin-sensitive tissues.

In most vertebrates, uptake and oxidation of
circulating sugars by locomotor muscles rises with increasing
exercise intensity. However, uptake rate by muscle plateaus
at moderate aerobic exercise intensities and intracellular
fuels dominate at oxygen consumption rates of 50 %
of maximum or more. Further, uptake and oxidation of circulating
fructose by muscle is negligible. In contrast, hummingbirds
and nectar bats are capable of fueling expensive
hovering flight exclusively, or nearly completely, with
dietary sugar. In addition, hummingbirds and nectar bats
appear capable of fueling hovering flight completely with
fructose. Three crucial steps are believed to be rate limiting
to muscle uptake of circulating glucose or fructose in
vertebrates: (1) delivery to muscle; (2) transport into muscle
through glucose transporter proteins (GLUTs); and (3)
phosphorylation of glucose by hexokinase (HK) within the
muscle. In this review, we summarize what is known about
the functional upregulation of exogenous sugar flux at each
of these steps in hummingbirds and nectar bats. High cardiac
output, capillary density, and blood sugar levels in hummingbirds and bats enhance sugar delivery to muscles
(step 1). Hummingbird and nectar bat flight muscle
fibers have relatively small cross-sectional areas and thus
relatively high surface areas across which transport can
occur (step 2). Maximum HK activities in each species are
enough for carbohydrate flux through glycolysis to satisfy
100 % of hovering oxidative demand (step 3). However,
qualitative patterns of GLUT expression in the muscle (step
2) raise more questions than they answer regarding sugar
transport in hummingbirds and suggest major differences
in the regulation of sugar flux compared to nectar bats.
Behavioral and physiological similarities among hummingbirds,
nectar bats, and other vertebrates suggest enhanced
capacities for exogenous fuel use during exercise may be
more wide spread than previously appreciated. Further,
how the capacity for uptake and phosphorylation of circulating
fructose is enhanced remains a tantalizing unknown.

The effects of camel milk (CM) intake on glycemic control in patients with diabetes are controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of CM intake on glucose homeostasis parameters in patients with both types of diabetes mellitus; T1DM and T2DM. We searched Google Scholar, PubMed/MEDLINE, EBSCO host, CINAHL, ScienceDirect, Cochrane, ProQuest Medical, Web of Science, and Scopus databases from inception until the end of November 2021. Relevant RCTs were identified, and the effect size was reported as mean difference (MD) and standard deviation (SD). Parameters of glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting serum insulin (FI), insulin resistance (expressed in terms of HOMA-IR), insulin dose (ID) received, serum insulin antibody (IA), and C-peptide (CP) were tested. Out of 4054 collected articles, 14 RCTs (total 663 subjects) were eligible fo...

Diabetes is expected to increase up to 700 million people worldwide with type 2 diabetes being the most frequent. The use of nutritional interventions is one of the most natural approaches for managing the disease. Minerals are of paramount importance in order to preserve and obtain good health and among them molybdenum is an essential component. There are no studies about the consumption of biofortified food with molybdenum on glucose homeostasis but recent studies in humans suggest that molybdenum could exert hypoglycemic effects. The present study aims to assess if consumption of lettuce biofortified with molybdenum influences glucose homeostasis and whether the effects would be due to changes in gastrointestinal hormone levels and specifically Peptide YY (PYY), Glucagon-Like Peptide 1 (GLP-1), Glucagon-Like Peptide 2 (GLP-2), and Gastric Inhibitory Polypeptide (GIP). A cohort of 24 people was supplemented with biofortified lettuce for 12 days. Blood and urine samples were obtain...

To compare endocrine, metabolic, and inflammatory changes induced by gastric bypass (GB) and sleeve gastrectomy (SG) in patients with type 2 diabetes mellitus (T2DM), and to investigate the mechanisms of success after metabolic surgery. Sixteen GB and 16 SG patients were followed up before and at 1 year after surgery. The 75-g oral glucose tolerance test (OGTT) was performed before and after surgery. Glucose homeostasis, serum interleukin-1, plasma gut hormones and adipokines, and the United Kingdom Prospective Diabetes Study (UKPDS) ten-year cardiovascular risks were evaluated. The diabetes remission rate was significantly higher in GB than SG. Changes in the area under the curve (AUC) for glucose were greater in those with complete and partial remission after GB and remitters after SG than non-remitters after SG, whereas changes in AUC for C-peptide were higher in complete and partial remitters after GB than non-remitters after SG. Insulinogenic index was enhanced and serum interleukin-1 was reduced in complete remit-ters after GB and remitters after SG. Logistic regression analysis confirmed that insulinogenic index and interleukin-1, not insulin resistance, were the factors determining the success of diabetes remission after metabolic surgeries. GB and SG significantly reduced the ten-year risk of coronary heart disease and fatal coronary heart disease in T2DM patients after surgery, while GB had the additional benefit of reduced stroke risk. Human diabetes remission after metabolic surgery is through insulin secretion and interleukin-1 dependent mechanisms. GB is superior to SG in cardiocerebral risk reduction in Asian non-morbidly obese, not well-controlled T2DM patients.

To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting insulin, a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in fasting plasma insulin (FI) levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-hour insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio=1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We ext...

Development of diabetes generally reflects an inadequate mass of insulin-producing beta-cells. beta-cell proliferation and differentiation are regulated by a variety of growth factors and hormones, including insulin-like growth factor I (IGF-I). GRF1 is a Ras-guanine nucleotide exchange factor known previously for its restricted expression in brain and its role in learning and memory. Here we demonstrate that GRF1 is also expressed in pancreatic islets. Interestingly, our GRF1-deficient mice exhibit reduced body weight, hypoinsulinemia and glucose intolerance owing to a reduction of beta-cells. Whereas insulin resistance is not detected in peripheral tissues, GRF1 knockout mice are leaner due to increased lipid catabolism. The reduction in circulating insulin does not reflect defective glucose sensing or insulin production but results from impaired beta-cell proliferation and reduced neogenesis. IGF-I treatment of isolated islets from GRF1 knockouts fails to activate critical downstream signals such as Akt and Erk. The observed phenotype is similar to manifestations of preclinical type 2 diabetes. Thus, our observations demonstrate a novel and specific role for Ras-GRF1 pathways in the development and maintenance of normal beta-cell number and function.

Invasive candidiasis poses a major healthcare threat. The human opportunistic fungal pathogen Candida glabrata, which causes mucosal and deep-seated infections, is armed with distinct virulence attributes, including a family of 11 glycosylphosphatidylinositol-linked aspartyl proteases, CgYapsins. Here, we have profiled total membrane proteomes of the C. glabrata wildtype and 11 proteases-deficient strain, Cgyps1-11Δ, by mass spectrometry analysis and uncovered a novel role for fungal yapsins in glucose sensing and homeostasis. Furthermore, through label-free quantitative membrane proteome analysis, we showed differential abundance of 42% of identified membrane proteins, with electron transport chain and glycolysis proteins displaying lower and higher abundance in Cgyps1-11Δ cells, compared with wildtype cells, respectively. We also demonstrated elevated glucose uptake and upregulation of genes that code for the low-glucose sensor CgSnf3, transcriptional regulators CgMig1 and CgRgt1, and hexose transporter CgHxt2/10 in the Cgyps1-11Δ mutant. We further elucidated a potential underlying mechanism through genetic and transcript measurement analysis under low- and high-glucose conditions and found CgSNF3 deletion to rescue high glucose uptake and attenuated growth of the Cgyps1-11Δ mutant in YPD medium, thereby linking CgYapsins with regulation of the CgSnf3-dependent low-glucose sensing pathway. Last, high ethanol production, diminished mitochondrial membrane potential, and elevated susceptibility to oxidative phosphorylation inhibitors point toward increased fermentative and decreased respiratory metabolism in the Cgyps1-11Δ mutant. Altogether, our findings revealed new possible glucose metabolism-regulatory roles for putative cell surface-associated CgYapsins and advanced our understanding of fungal carbohydrate homeostasis mechanisms.

To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting insulin, a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in fasting plasma insulin (FI) levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-hour insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio=1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We ext...

Glucagon is a 29-amino acid polypeptide released from pancreatic islet α-cells that acts to maintain euglycemia by stimulating hepatic glycogenolysis and gluconeogenesis. Despite its importance, there remains controversy about the mechanisms responsible for glucagon clearance in the body. In the current study, enzymatic metabolism of glucagon was assessed using sensitive mass spectrometric techniques to identify the molecular products. Incubation of glucagon with purified porcine dipeptidyl peptidase IV (DP IV) yielded sequential production of glucagon3–29 and glucagon5–29. In human serum, degradation to glucagon3–29 was rapidly followed by N-terminal cyclization of glucagon, preventing further DP IV-mediated hydrolysis. Bioassay of glucagon, following incubation with purified DP IV or normal rat serum demonstrated a significant loss of hyperglycemic activity, while a similar incubation in DP IV-deficient rat serum did not show any loss of glucagon bioactivity. Degradation, monitored by mass spectrometry and bioassay, was blocked by the specific DP IV inhibitor, isoleucyl thiazolidine. These results identify DP IV as a primary enzyme involved in the degradation and inactivation of glucagon. These findings have important implications for the determination of glucagon levels in human plasma.

Obesity can lead to chronic inflammation in different tissues including the adipose tissue, liver, pancreas, and brain. This inflammatory process generates insulin and leptin resistance, as well as alterations in glucose and lipid metabolism, leading to the development of degenerative diseases including type II diabetes. Additionally, the inhibition of inflammatory signaling can prevent the development of obesity and restore insulin sensitivity. Different studies have shown that an enriched environment (EE) has beneficial effects on learning and memory via enhancing central nervous system activity. Housing in an EE also regulates the differentiation and activation of immune cells and reduces inflammation in different disease models. Therefore, in the current study we explore whether an EE is capable of restoring energy balance in obese mice that previously presented metabolic alterations. We discovered that an EE improved glucose metabolism, increased insulin signaling in the liver,...

Aqueous extracts of some antidiabetic Ayurvedic plant treatments such as Trigonella foenum-graecum Linn (TFG), Pterocarpus marsupium Roxb (PM), Gymnema sylvestre R.Br (GS) and Curcuma longa Linn (CL) were tested for their biological effects on glucose uptake by mouse muscle tissue and insulin secretion from mouse pancreas under both basal and hyperglycemic culture conditions. The results indicate that none of these treatments have a significant effect on either glucose uptake by muscle or insulin secretion from the pancreas under basal conditions. Under hyperglycemic conditions all treatments except GS demonstrate significant effects on glucose uptake by muscle tissue, and all treatments were effective at increasing insulin secretion from pancreas. This suggests that all these plant treatments enhance glucose homeostasis by stimulating either insulin secretion (GS) or enhancing glucose uptake (TFG) or activating both (CL and PM).
Keywords: Ayurvedic Medicinal Plants; Diabetes; Insulin Secretion; Glucose Uptake.