Saxagliptin, a selective dipeptidyl peptidase-4 inhibitor, alleviates somatic cell aneugenicity and clastogenicity in diabetic mice.

Diabetes-related complications are becoming increasingly common as the global prevalence of diabetes increases. Diabetes is also linked to a high risk of developing cancer. This raises the question of whether cancer vulnerability is caused by diabetes itself or the use of antidiabetic drugs. Chromosomal instability, a source of genetic modification involving either an altered chromosomal number or structure, is a hallmark of cancer. Saxagliptin has been approved by the FDA for diabetes treatment. However, the detailed in vivo effects of prolonged saxagliptin treatment on chromosomal instability have not yet been reported. In this study, streptozotocin was used to induce diabetes in mice, and both diabetic and non-diabetic mice received saxagliptin for five weeks. Fluorescence in situ hybridization was conducted in combination with a bone marrow micronucleus test for measuring chromosomal instability. Our results indicated that saxagliptin is neither mutagenic nor cytotoxic, under the given treatment regimen. Diabetic mice had a much higher incidence of micronuclei formation, and a centromeric DNA probe was present inside the majority of the induced micronuclei, indicating that most of these were caused by chromosome nondisjunction. Conversely, diabetic mice treated with saxagliptin exhibited a significant decrease in micronuclei induction, which were centromeric-positive and centromeric-negative. Diabetes also causes significant biochemical changes indicative of oxidative stress, such as increased lipid peroxidation and decreased reduced/oxidized glutathione ratio, which was reversed by saxagliptin administration. Overall, saxagliptin, the non-mutagenic antidiabetic drug, maintains chromosomal integrity in diabetes and reduces micronuclei formation by restoring redox imbalance, further indicating its usefulness in diabetic patients.

Failure to replicate the diabetes alleviating effect of a maternal gluten-free diet in non-obese diabetic mice.

Type 1 diabetes (T1D) is an autoimmune disease with an unexplained rising incidence for which environmental factors like gluten may play a role. Previously, we showed that a gluten-free (GF) diet provided strictly in utero reduces the autoimmune diabetes incidence in Non-Obese Diabetic (NOD) mice compared to a gluten-containing standard (STD) diet. The current study was initiated to elucidate possible mechanisms behind the diabetes-alleviating effect of the same diet intervention. NOD mice received either a GF Altromin diet or a STD Altromin diet during pregnancy. Female offspring from both groups were fed a STD diet throughout life and their diabetes incidence was recorded for 200 days. The following parameters were measured in 13-week-old female offspring: insulitis degree, glucose and insulin tolerance, and plasma insulin autoantibody titer. The diet intervention showed no reduction in autoimmune diabetes incidence, insulitis degree, glucose nor insulin tolerance and plasma insulin autoantibody titer. In conclusion, this study could not replicate the previously observed diabetes alleviative effects of a maternal gluten-free diet in NOD mouse offspring and could therefore not further elucidate potential mechanisms.

The effect of balanities aeqyptiaca defatted protein meal and protein concentrate supplemented diet on biochemical and molecular stability of diabetic wister albino rat.

Balanites aeqyptiaca (BA) seeds were toasted at 70 °C, milled and the oil expelled to resolve to meal which were defatted to resolve to defatted balanites aeqyptiaca (BA) protein meal and (BA) protein concentrate respectively. These were subjected to analysis using standard methods. There exist marked trend between defatted balanites aeqyptiaca protein meal, protein concentrate and incidences of diabetes. This work investigated the anti- diabetic effects of balanites aeqyptiaca defatted protein meal and concentrate supplemented diets in streptozotocin (STZ)-induced diabetic rats. The rats were fattened for two weeks with high fat diet (HFD) to introduce Hyperglycemia and then made diabetic by intraperitoneal administration of STZ (35 mg/kg body weight) and fed diets containing 5 % defatted balanites aeqyptiaca protein meal (DAPM) and 5 % balanites aeqyptiaca protein concentrate (APC) for 14 days. The effect of the diet on blood glucose, serum glutathione peroxidase (GPx), glutathione transferase (GSH), thiobarbituric acid reactive species (TBARS), α-amylase and intestinal α-glucosidase activities were investigated. There was marked increase in the blood glucose, TBARS, pancreatic α-amylase and intestinal α-glycosidase with corresponding decrease in serum GPx and GSH contents in diabetic rats control groups. These trends were however, reversed in diabetic rats fed diet supplemented with the balanites aeqyptiaca protein meals for 14 days. The meals from defatted and protein concentrate inhibit α-amylase and α-glycosidase inhibitory activity in vivo. Thus, the anti-diabetes properties of the defatted meal and protein concentrate may be attributed to the influence of its constituent phytochemicals on starch digestion as well as endogenous enzymes activities. The study revealed that defatted aduwa meal and proteins concnentrate demonstrated potentials used as functional ingredients in food materials and could also increase income access of low resource populace.

Dietary Blueberry Ameliorates Vascular Complications in Diabetic Mice Possibly through NOX4 and Modulates Composition and Functional Diversity of Gut Microbes.

SCOPE: In diabetes, endothelial inflammation and dysfunction play a pivotal role in the development of vascular disease. This study investigates the effect of dietary blueberries on vascular complications and gut microbiome in diabetic mice. METHODS AND RESULTS: Seven-week-old diabetic db/db mice consume a standard diet (db/db) or a diet supplemented with 3.8% freeze-dried blueberry (db/db+BB) for 10 weeks. Control db/+ mice are fed a standard diet (db/+). Vascular inflammation is assessed by measuring monocyte binding to vasculature and inflammatory markers. Isometric tension procedures are used to assess mesenteric artery function. db/db mice exhibit enhanced vascular inflammation and reduced endothelial-dependent vasorelaxation as compared to db/+ mice, but these are improved in db/db+BB mice. Blueberry supplementation reduces the expression of NOX4 and IκKß in the aortic vessel and vascular endothelial cells (ECs) isolated from db/db+BB compared to db/db mice. The blueberry metabolites serum reduces glucose and palmitate induced endothelial inflammation in mouse aortic ECs. Further, blueberry supplementation increases commensal microbes and modulates the functional potential of gut microbes in diabetic mice. CONCLUSION: Dietary blueberry suppresses vascular inflammation, attenuates arterial endothelial dysfunction, and supports the growth of commensal microbes in diabetic mice. The endothelial-specific vascular benefits of blueberries are mediated through NOX4 signaling.

Physicochemical Properties of the Soluble Dietary Fiber from Laminaria japonica and Its Role in the Regulation of Type 2 Diabetes Mice.

Laminaria japonica is a large marine brown alga that is annually highly productive. However, due to its underutilization, its potential value is substantially wasted. For example, a lot of Laminaria japonica cellulose remains unused during production of algin. The soluble dietary fiber (SDF) was prepared from the byproducts of Laminaria japonica, and its physicochemical properties were explored. SDF exhibits good water-holding, oil-holding, water-absorbing swelling, glucose and cholesterol absorption capacity, and inhibitory activity of α-amylase and α-glucosidase. In addition, the beneficial effects of SDF in diabetic mice include reduced body weight, lower blood glucose, and relieved insulin resistance. Finally, the intestinal flora and metabolomic products were analyzed from feces using 16S amplicon and LC-MS/MS, respectively. SDF not only significantly changed the composition and structure of intestinal flora and intestinal metabolites, but also significantly increased the abundance of beneficial bacteria Akkermansia, Odoribacter and Bacteroides, decreased the abundance of harmful bacteria Staphylococcus, and increased the content of bioactive substances in intestinal tract, such as harmine, magnolol, arachidonic acid, prostaglandin E2, urimorelin and azelaic acid. Taken together, these findings suggest that dietary intake of SDF alleviates type 2 diabetes mellitus disease, and provides an important theoretical basis for SDF to be used as a functional food.

The potential therapeutic effects of Trifolium alexandrinum extract, hesperetin and quercetin against diabetic nephropathy via attenuation of oxidative stress, inflammation, GSK-3ß and apoptosis in male rats.

Diabetic nephropathy (DN) is one of the manifestations of systemic microangiopathy in diabetes. Trifolium alexandrinum extract (TAE) contains biologically active phenolic compounds such as hesperetin (HES) and quercetin, possess various pharmacological properties, including anti-inflammatory, and anti-oxidative potentials. The present study aimed to assess the therapeutic effects and mechanisms underlying the anti-diabetic, antioxidant, and anti-inflammatory effects of HES and quercetin extracted from TAE, and TAE in STZ-induced DN. Male albino rats (170 ± 10 g) were divided into group (1); control rats and groups (2-5); diabetic/HFD were intraperitoneal (i.p.) injected with STZ (35 mg/kg), diabetic rats were randomly classified into STZ, STZ + HES (40 mg/kg), STZ + quercetin (50 mg/kg), and STZ + TAE (200 mg/kg) groups. After 5 weeks, blood and kidney samples were collected for further biochemical, western blotting and histopathological studies. Serum renal functions, renal oxidative status biomarkers and proinflammatory cytokines were determined. The results revealed that there were significant increases in urea, BUN, creatinine, ALP, total protein, albumin, and globulin with a significant decrease in Na+ and K+ levels, as well as significant elevation in TBARS, TGF-ß, TNF-α, IL-6 and the expression levels of GSK-3ß, as well as significant decline in TAC, GSH and CAT levels in STZ-treated group compared to the control rats. The previous deleterious alterations were significantly ameliorated after the treatment of diabetic rats with HES, quercetin and TAE. In conclusion, our data demonstrated that HES, quercetin and TAE could be used as potent therapeutic agents to counter DN through antioxidant, anti-inflammatory, and antidiabetic effects.

Insulin receptors in the CA1 field of hippocampus and selected blood parameters in diabetic rats fed with bilberry fruit.

INTRODUCTION: Bilberry fruit is believed to be a promising factor in the treatment of diabetes mellitus. Chronic hyperglycaemia affects the function of the central nervous system, which may be manifested as changes in hypothalamic insulin signalling. MATERIAL AND METHODS: Using DPPH and ABTS assays, total phenolic content in bilberry fruit and its antioxidant activities were examined. The selected biochemical parameters of blood (glucose, fructosamine, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides), as well as the expression of insulin receptors, were studied in the hippocampal CA1 field of healthy and diabetic (streptozotocin-induced; 60 mg kg-1 body weight) Wistar rats fed with bilberry fruit (16 g kg-1 body weight per day; 6 weeks), as well as of the corresponding control groups. RESULTS: Biochemical analyses revealed ambiguous results, but a significantly (P<0.05) decrease in the level of LDL-cholesterol was observed in the group of healthy rats supplemented with bilberry pulp after 6 weeks of the treatment. There was also a difference (P<0.05) in the level of LDL-cholesterol in the mentioned healthy animals fed with bilberry, versus the healthy control group. An increased number of insulin receptors-immunoreactive neurons as well as nerve fibres in the CA1 field of diabetic rats fed with bilberry fruit was also found. CONCLUSIONS: An inclusion of bilberry fruit in the daily diet during the course of diabetes can lead to plasticity of hippocampal neurons/nerve fibres, manifested by changes in insulin receptors expression. Whether or not the observed changes had protective effects (by reducing damages caused by diabetes mellitus) on the function of the central nervous system neurons needs further study.

Mfsd2a overexpression alleviates vascular dysfunction in diabetic retinopathy.

Diabetic retinopathy (DR) is one of the common complications in diabetic patients. Nowadays, VEGF pathway is subject to extensive research. However, about 27% of the patients have a poor visual outcome, with 50% still having edema after two years' treatment of diabetic macular edema (DME) with ranibizumab. Docosahexaenoic acid (DHA), the primary ω-3 long-chain polyunsaturated fatty acid (LC-PUFA), reduces abnormal neovascularization and alleviates neovascular eye diseases. A study reported that fish oil reduced the incidence of retinopathy of prematurity (ROP) by about 27.5% in preterm infants. Although ω-3 LC-PUFAs protects against pathological retinal neovascularization, the treatment effectiveness is low. It is interesting to investigate why DHA therapy fails in some patients. In human vitreous humor samples, we found that the ratio of DHA and DHA-derived metabolites to total fatty acids was higher in vitreous humor from DR patients than that from macular hole patients; however, the ratio of DHA metabolites to DHA and DHA-derived metabolites was lower in the diabetic vitreous humor. The expression of Mfsd2a, the LPC-DHA transporter, was reduced in the oxygen-induced retinopathy (OIR) model and streptozotocin (STZ) model. In vitro, Mfsd2a overexpression inhibited endothelial cell proliferation, migration and vesicular transcytosis. Moreover, Mfsd2a overexpression in combination with the DHA diet obviously reduced abnormal retinal neovascularization and vascular leakage, which is more effective than Mfsd2a overexpression alone. These results suggest that DHA therapy failure in some DR patients is linked to low expression of Mfsd2a, and the combination of Mfsd2a overexpression and DHA therapy may be an effective treatment.

Glavonoid-rich oil supplementation reduces stearoyl-coenzyme A desaturase 1 expression and improves systemic metabolism in diabetic, obese KK-Ay mice.

AIMS: Glavonoid-rich oil (GRO) derived from ethanol extraction of licorice (Glycyrrhiza glabra Linne) root has been reported to have beneficial effects on health. In this study, we aimed to determine the effect of long-term administration of GRO on metabolic disorders and to elucidate the molecular mechanism. MAIN METHODS: Female obese, type 2 diabetic KK-Ay mice were fed diets supplemented with 0.3% or 0.8% GRO (w/w) for 4-12 weeks. Mice were euthanized and autopsied at 20 weeks old. The effects of GRO on lipid and glucose metabolism were evaluated by measuring physiological and biochemical markers using mRNA sequencing, quantitative reverse-transcription PCR, and western blot analyses. KEY FINDINGS: Compared to mice fed the control diet, GRO-supplemented mice had reduced body and white adipose tissue weights, serum levels of triglycerides and cholesterol, and improved glucose tolerance, while food intake was not affected. We found remarkable reductions in the gene expression levels of stearoyl-coenzyme A desaturase 1 (Scd1) and pyruvate dehydrogenase kinase isoenzyme 4 (Pdk4) in the liver, in addition to decreased expression of fatty acid synthase (Fasn) in inguinal white adipose tissue (iWAT). These results suggest that GRO supplementation improves lipid profiles via reduced de novo lipogenesis in the liver and white adipose tissue. Glucose metabolism may also be improved by increased glycolysis in the liver. SIGNIFICANCE: Our analysis of long-term supplementation of GRO in obese and diabetic mice should provide novel insight into preventing insulin resistance and metabolic syndromes.

Opuntia dillenii (Ker Gawl.) Haw., Seeds Oil Antidiabetic Potential Using In Vivo, In Vitro, In Situ, and Ex Vivo Approaches to Reveal Its Underlying Mechanism of Action.

Opuntia dillenii Ker Gawl. is one of the medicinal plants used for the prevention and treatment of diabetes mellitus (DM) in Morocco. This study aims to investigate the antihyperglycemic effect of Opuntia dillenii seed oil (ODSO), its mechanism of action, and any hypoglycemic risk and toxic effects. The antihyperglycemic effect was assessed using the OGTT test in normal and streptozotocin (STZ)-diabetic rats. The mechanisms of action were explored by studying the effect of ODSO on the intestinal absorption of d-glucose using the intestinal in situ single-pass perfusion technique. An Ussing chamber was used to explore the effects of ODSO on intestinal sodium-glucose cotransporter 1 (SGLT1). Additionally, ODSO's effect on carbohydrate degrading enzymes, pancreatic α-amylase, and intestinal α-glucosidase was evaluated in vitro and in vivo using STZ-diabetic rats. The acute toxicity test on mice was performed, along with a single-dose hypoglycemic effect test. The results showed that ODSO significantly attenuated the postprandial hyperglycemia in normal and STZ-diabetic rats. Indeed, ODSO significantly decreased the intestinal d-glucose absorption in situ. The ex vivo test (Ussing chamber) showed that the ODSO significantly blocks the SGLT1 (IC50 = 60.24 µg/mL). Moreover, ODSO indu\ced a significant inhibition of intestinal α-glucosidase (IC50 = 278 ± 0.01 µg/mL) and pancreatic α-amylase (IC50 = 0.81 ± 0.09 mg/mL) in vitro. A significant decrease of postprandial hyperglycemia was observed in sucrose/starch-loaded normal and STZ-diabetic ODSO-treated rats. On the other hand, ODSO had no risk of hypoglycemia on the basal glucose levels in normal rats. Therefore, no toxic effect was observed in ODSO-treated mice up to 7 mL/kg. The results of this study suggest that ODSO could be suitable as an antidiabetic functional food.

Gut modulation based anti-diabetic effects of carboxymethylated wheat bran dietary fiber in high-fat diet/streptozotocin-induced diabetic mice and their potential mechanisms.

We explored the effect of carboxymethylated wheat bran dietary fibers (DFs) on mice with type 2 diabetes (T2D) (induced by HFD combined with STZ) and their possible hypoglycemic mechanism. After feeding the diabetic mice with modified DFs for four weeks, the DFs had lipid lowering and anti-hyperglycemic effect, via increasing the levels of insulin, GLP-1, PYY, and SCFAs in diabetic mice, and improving the histopathology of liver and pancreas. qRT-PCR results showed that the intake of DFs up-regulated the expression levels of G6Pase and Prkce, and down regulated the expression levels of Glut2 and InsR in the liver of diabetic mice. It is suggested that DFs may play a role by inhibiting 1,2-DAG-PKCε pathway, improving insulin receptor activity and insulin signal transduction. 16 S rDNA high-throughput sequencing results showed that the DFs significantly improved the relative abundance of Akkermansia muciniphila, increased the diversity of gut microbiota and reduced the ratio of Firmicutes to Bacteroidetes, thus promoting the hypoglycemic and hypolipidemic effect on diabetic mice. Our study can foster the further understanding of the gut modulatory biomarkers and related metabolites, and may extend the basis for DFs as a potential dietary intervention to prevent or treat the T2D.

Characterization of Anoectochilus roxburghii polysaccharide and its therapeutic effect on type 2 diabetic mice.

Anoectochilus roxburghii is a traditional herb in China that can be potentially used to treat diabetes. A novel polysaccharide ARLP-W was isolated from Anoectochilus roxburghii by chromatography on DEAE-52 cellulose. Chemical analysis indicated that ARLP-W (8.1 × 104 Da) was mainly composed of mannose and glucose. The main linkages of glycosidic bonds of ARLP-W were ß-1, 4-Manp and α-1, 4-Glcp. The terminal Glcp was connected to Manp-via O-3. RT-qPCR and western blotting analysis showed that ARLP-W caused a significant reduction in the levels of the key gluconeogenesis enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) in the liver. The results of the insulin resistance tests indicated that ARLP-W increased glucose absorption. These results indicate that ARLP-W has a good therapeutic effect on type 2 diabetes and can assist with further development and application treatment of diabetes.

Oral administration of mangiferin ameliorates diabetes in animal models: a meta-analysis and systematic review.

Although mangiferin has a number of documented beneficial effects, there are no systematic reviews or meta-analyses of its effects in diabetic animal models. To investigate the effects of oral administration of mangiferin on blood glucose levels, body weight, and total cholesterol and triglycerides levels in diabetic animal models, a meta-analysis was conducted and the underlying mechanisms were reviewed. Studies from 6 databases (PubMed, Web of Science, Embase, Cochrane Library, and CNKI (China National Knowledge Infrastructure), and Wanfang Med) were searched from inception to April 2020. After article screening, a total of 19 articles were included in this meta-analysis. The meta-analysis was performed using RevMan 5.3 and STATA 14.0 software. The overall pooled estimate of standardized mean difference (SMD) of mangiferin's effect on blood glucose was -1.27 (95% confidence interval [CI]: -1.71, -0.82, P < .00001). Body weight increased in lean diabetic animals with an SMD of 1.41 (95% CI: 0.57, 2.25; P = .001), while it decreased in obese diabetic animals with an SMD of -0.92 (95% CI: -1.69, -0.14; P = .02). Mangiferin intake reduced serum total cholesterol and triglycerides levels with SMDs of -1.02 (95% CI: -1.43, -0.61; P < .001) and -1.24 (95% CI: -1.70, -0.79; P < .001), respectively. The meta-analysis suggests that oral intake of mangiferin has a significant antidiabetic effect in animal models, and the systematic review suggested that this function might be attributed to its anti-inflammatory and antioxidative properties, as well as to its function of improving glycolipid metabolism and enhancing insulin signaling.

A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome-Intestine-Pancreas Axis.

The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be administered daily are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially available yogurt (control yogurt). Interestingly, we found that the feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the gut microbiota composition compared to milk, while the control yogurt negatively modulated it by significantly increasing the abundance of detrimental bacteria such as Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected pancreatic islet morphology compared to the milk control, while the control yogurt demonstrated worse effects on islets. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a therapeutic to prevent diabetes progression.

Goat Milk Improves Glucose Homeostasis via Enhancement of Hepatic and Skeletal Muscle AMP-Activated Protein Kinase Activation and Modulation of Gut Microbiota in Streptozocin-Induced Diabetic Rats.

SCOPE: Previously, the metabolic benefits of goat milk consumption in high-fat diet-fed rats are demonstrated. However, the effects are only reported in one animal model and the involvement of gut microbiota is not investigated. The aim of this study is to investigate the effects of goat milk consumption on glucose homeostasis and gut microbiota in streptozocin (STZ)-induced diabetic rats. METHODS AND RESULTS: STZ-induced diabetic rats are fed with three dosages of goat milk: 2.5, 5, and 10 g kg-1 . Parameters related to glucose homeostasis, hepatic and skeletal muscle AMP-activated protein kinase (AMPK) activation, and gut microbiota are investigated. The dose of 10 g kg-1 exerts more metabolic benefits. Goat milk consumption improves fasting glucose levels, glucose tolerance, insulin sensitivity, and promotes hepatic and skeletal muscle AMPK activation in STZ-injected diabetic rats. Goat milk modulates gut microbiota, increases the relative abundance of Lactobacillus, and augments levels of propionic and butyric acids. CONCLUSION: This study demonstrates the metabolic benefits of goat milk consumption in STZ-induced diabetic rats, which is consistent with the previous observations in high-fat diet-induced diabetic rats. Furthermore, this study elucidates the modulation of gut microbiota by goat milk, which likely mediates the metabolic effects of goat milk.

Dietary low ratio of n-6/n-3 polyunsaturated fatty acids improve type 2 diabetes mellitus via activating brown adipose tissue in male mice.

The ratio n-6/n-3 polyunsaturated fatty acids (PUFA) has been caused widespread discussion. However, the best ratio and mechanism of n-6/n-3 PUFA in type 2 diabetes mellitus (T2DM) are largely unknown. This study investigated the effects of different ratio of n-6/n-3 PUFA diets on brown adipose tissue (BAT) and T2DM in mice. Results showed that compared with high ratio of n-6/n-3 PUFA (50:1) diet, lower ratio of n-6/n-3 PUFA (1:1 and 5:1) diets significantly increased BAT mass by 67.55% and 60.49%, decreased the fasting blood glucose (24.87% and 20.64%), total cholesterol (32.9% and 23.84%), triglyceride (33.51% and 29.62%), low-density lipoprotein cholesterol (19.23% and 17.38%), and increased glucose tolerance by 21.99% and 15.52%. Further, qRT-PCR analyses indicated that lower ratio of n-6/n-3 PUFA diets activated BAT, increased the expression of Ucp1, ß-3AR, PPAR-γ, cAMP, GLU1, HSL, LPL, and PGC-1α, further improved lipid and glucose metabolism in T2DM mice. In conclusion, this study substantiated that the lower ratio of n-6/n-3 PUFA (1:1 and 5:1) improve symptoms associated with T2DM via activating BAT. PRACTICAL APPLICATION: Dietary ratio of n-6/n-3 polyunsaturated fatty acids is essential for the improvement of chronic diseases. Our current study showed that 1:1 or 5:1 ratio of n-6/n-3 polyunsaturated fatty acids had better efficiency for type 2 diabetes mellitus via activating brown adipose tissue when compared with 1:50. This finding provided useful guidance for the daily diet of patients with diabetes.

Protein Isolates from Raw and Cooked Foxtail Millet Attenuate Development of Type 2 Diabetes in Streptozotocin-Induced Diabetic Mice.

SCOPE: Millet protein has received much attention due to its beneficial role in alleviating metabolic disease symptoms. This study aims to investigate the role and molecular mechanism of foxtail millet protein isolates, including protein isolates from raw and cooked foxtail millet in alleviating diabetes, including gut microbiota and intracellular signal pathways. METHODS AND RESULTS: Protein isolates from raw and cooked foxtail millet are orally administered to streptozotocin (STZ)-induced diabetic mice for 5 weeks before hypoglycemic effect evaluation. The results show that foxtail millet protein isolates improve glucose intolerance and insulin resistance in diabetic mice. However, only the protein isolate from cooked foxtail millet reverse the weight loss trend and alleviate lipid disorders in diabetic mice. Besides, 16S rRNA sequencing show that both raw and cooked foxtail millet protein isolates altered diabetes-induced gut dysbiosis. In addition, western blotting analysis indicated that the protein isolate from cooked foxtail millet increases the expression levels of glucagon-like peptide-1 receptor (GLP-1R), phosphoinositide 3-kinase (PI3K), and phosphoinositide-protein kinase B (p-AKT)/AKT while the protein isolate from raw foxtail millet downregulates stearoyl-coenzyme A desaturase 1 (SCD1) level. CONCLUSION: Both raw and cooked foxtail millet protein isolates can exert hypoglycemic effects in diabetic mice through rewiring glucose homeostasis, mitigating diabetes-induced gut dysbiosis, and affecting the GLP-1R/PI3K/AKT pathway.

Anti-Diabetic Obesity Effects of Wasabia Japonica Matsum Leaf Extract on 45% Kcal High-Fat Diet-Fed Mice.

The present study examined the effects of Wasabi leaf (WL) on 45% Kcal high-fat diet (HFD)-fed mild diabetic obese mice. In particular, the hepatoprotective (i.e., liver weight, histopathology of liver, serum aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase) effects of 12 weeks of continuous oral administration of 250 mg/kg metformin, and 200, 100, or 50 mg/kg WL were investigated. In addition, the hypolipidemic (i.e., serum triglyceride, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein levels), hypoglycemic (i.e., glycated hemoglobin, blood glucose and insulin levels, pancreatic weight, and immunohistochemical-histopathological analysis of the pancreas), and anti-obesity effects (i.e., body weight, mean food consumption, total and abdominal body fat mass, periovarian fat weight, and histopathology of the periovarian and abdominal wall adipocytes) were monitored. The liver and general antioxidant defense systems were also assessed by lipid metabolism-related gene expression. All diabetes manifestations and related complications, including obesity and non-alcoholic fatty liver disease (NAFLD), were dose-dependently reduced after 84 days of oral treatment with metformin or each of the three dosages of WL. In particular, 50 mg/kg WL showed effective suppression effects against HFD-induced diabetes and related complications of obesity, NAFLD, and hyperlipidemia, comparable to the effects of metformin.

Effects of Different n6/n3 PUFAs Dietary Ratio on Cardiac Diabetic Neuropathy.

We studied the influence of experimentally induced DM1, in combination with different dietary n6:n3 polyunsaturated fatty acid (PUFA) ratios on different types of nerve fibers in rat myocardium, in order to reveal whether protective/unfavorable effects of different PUFAs on myocardial function in diabetic patients could be a (partial) repercussion of their effect on the changes in cardiac innervation. The control group (c) and diabetic group (stz) were fed with an n6/n3 ratio of ≈7; the diet of the stz+n6 group had an n6/n3 ratio ≈60, while the diet for the stz+DHA group contained 2.5% of fish oil (containing 16% eicosapentaenoic acid-EPA and 19% docosahexaenoic acid-DHA), n6/n3 ratio of ≈1. DM1 was induced by i.p. injection of streptozotocin (55 mg/kg) and rats were euthanized 30 days after induction. Immunohistochemistry was used for the detection and quantification of different types of neuronal fibers in the cardiac septum. We found changes in cardiac innervations characteristics for the initial phase of experimental DM1, which manifested as an increase in total number and area density of all neuronal fibers, measured by Pgp9.5 immunoreactivity. By detailed analysis, we found that this increase consisted mostly of heavy myelinated NF200 immunoreactive fibers and TH immunoreactive sympathetic fibers, while the density of ChAT immunoreactive parasympathetic fibers decreased. In the deep (middle) part of the myocardium, where rare fibers (of all studied types) were found, significant differences were not found. Surprisingly, we found a more consistent protective effect of n6 PUFAs, in comparison to n3 PUFAs supplementation. These results may provide a better understanding of the potential impacts of different PUFA ratios in the diet of diabetic patients on cardiac innervation and genesis and outcome of diabetic autonomic cardiomyopathy.

Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission.

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling.