Metabolism open最新文献

Background

Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme involved in alcohol metabolism. ALDH2 polymorphism has been reported as a risk factor for type 2 diabetes mellitus (T2DM) and is associated with liver insulin resistance due to alcohol consumption in non-diabetic individuals. Herein, we investigated the association between ALDH2 polymorphisms and insulin resistance in patients with T2DM.

Methods

We performed a meal tolerance test and the hyperinsulinemic-euglycemic clamp on 71 Japanese participants: 34 patients with T2DM, and 37 non-diabetic participants. We analyzed the ALDH2 polymorphism (ALDH2 rs67); GG type was defined as the T2DM high-risk group, compared with the low-risk AG and AA groups.

Results

Glucose levels were similar in the high- and low-risk T2DM groups. The high-risk group for T2DM showed a significantly higher BMI (p < 0.005), insulin resistance in HOMA-IR (p < 0.05), and Insulin sensitivity index (p < 0.05); however, there were no significant differences in insulin resistance in the clamp test (p = 0.10). Alcohol consumption did not differ significantly between groups (p = 0.66). Non-diabetic participants also showed higher HOMA-IR insulin resistance in the high-risk group (p < 0.05), but insulin resistance levels in the glucose clamp tests (p = 0.56) and insulin secretion were not significant.

Conclusion

The results suggest that ALDH2 is an important gene associated with insulin resistance and obesity in Japanese patients with type 2 diabetes.

Background

Tapinanthus dodoneifolius is a plant used in traditional African medicine to treat diabetes mellitus. This study aimed to evaluate the preventive antidiabetic potential of the aqueous extract of T. dodoneifolius leaves (AETD) in insulin resistant rats.

Methods

A quantitative phytochemical study of AETD was carried out to determine the contents of total phenols, tannins, flavonoids, and saponins. AETD was tested in vitro on the activity of α-amylase and α-glucosidase enzymes. Insulin resistance was induced for 10 days by daily subcutaneous injection of dexamethasone (1 mg/kg). One hour before, the rats were divided into 5 groups and treated as follows: group 1 received distilled water (10 mL/kg); group 2 received metformin (40 mg/kg), and groups 3, 4, and 5 were treated with AETD (125, 250, and 500 mg/kg). Body weight, blood sugar, food and water consumption, serum insulin level, lipid profile, and oxidative status were assessed. One-way analysis of variance followed by Turkey's post-test and two-way analysis followed by Bonferroni's post-test were used to analyze univariate and bivariate parameters, respectively.

Results

Results showed that the phenol content of AETD (54.13 ± 0.14 mg GAE/g extract) was higher than that of flavonoids (16.73 ± 0.06 mg GAE/g extract), tannins (12.08 ± 0.07 mg GAE/g extract), and saponins (IC₅₀ = 13.56 ± 0.03 mg DE/g extract). AETD showed a higher inhibitory potential on α-glucosidase activity (IC₅₀ = 191.51 ± 5.63 μg/mL) than on α-amylase activity (IC₅₀ = 1774.90 ± 10.32 μg/mL). AETD (250 and/or 500 mg/kg) prevented drastic loss of body weight and reduced food and water consumption in insulin resistant rats. The levels of blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and malondialdehyde were also reduced while high-density lipoprotein cholesterol level, reduced glutathion level, and catalase and superoxide dismutase activity increased after administration of AETD (250 and 500 mg/kg) in insulin resistant rats.

Conclusion

AETD has significant antihyperglycemic, antidyslipidemic, and antioxidant potential, thus it can be used for the management of type 2 diabetes mellitus and its complications.

Background

This meta-analysis was conducted to investigate the effects of incretin-based therapeutic agents, including the latest agent tirzepatide, on renal outcomes in patients with type 2 diabetes.

Methods

MEDLINE (via PubMed) and Cochrane databases were searched for studies involving incretin-based therapeutic agents up to July 2022. Randomized and controlled trials comparing incretin-based therapeutic agents with placebo or other antidiabetic agents, and reporting renal outcomes were selected. The inclusion criteria were items related to the effects on albuminuria and the kidney-specific composite outcomes. A network meta-analysis was conducted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

Twelve trials consisting of 75,346 participants were included in this meta-analysis. Glucagon-like peptide-1 (GLP-1) receptor agonists reduced the risk of the kidney-specific composite outcome by 21% (HR 0.79, 95% CI 0.75–0.85), and worsening albuminuria by 24% (HR 0.76, 95% CI 0.71–0.82). In particular, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide remarkably reduced the risk of the kidney-specific composite outcome by 45% (HR 0.55, 95% CI 0.40–0.77), and worsening albuminuria by 62% (HR 0.38, 95% CI 0.24–0.61).

Conclusions

Among incretin-based therapeutic agents, tirzepatide was associated with a significantly reduced risk of diabetic kidney disease.

Sodium butyrate (NaB), a short chain fatty acid (SCFA) has been shown to improve metabolic, glucose and lipid signaling. High fat diet elicits increased risk of cardiometabolic disease due to dysmetabolism, altered endothelial function and elevated oxidant activities. This study aims at evaluating the effect of NaB on high fat diet-fed female Wistar rats, and the possible role of vascular endothelial growth factor (VEGF). Twenty female Wistar rats with mean weight of 120 ± 5 g were divided randomly after one week of acclimatization into four groups: Control diet (CTR), High fat diet (HFD), NaB (200 mg/kg), and HFD + NaB. After six weeks of the experimental procedure, blood samples were collected by cardiac puncture. Data were analyzed and expressed in mean ± SEM and p-values <0.05 were accepted as significant. Data showed that HFD increased lactate dehydrogenase (LD) and free fatty acid (FFA), but not triglyceride (TG) and total cholesterol (TC). It also led to insulin resistance (elevated fasting blood glucose, insulin and homeostasis model assessment for insulin resistance). These effects of HFD were accompanied by increased lipid peroxidation (malondialdehyde and 4-hydroxynonenal). Sodium butyrate significantly decreased circulating nitric oxide (NO) and LD while increasing FFA, TG, insulin resistance, aggravated lipid peroxidation and increased VEGF in HFD rats (P < 0.05). We speculated therefore, that NaB aggravated glucose dysregulation and dyslipidemia, which is accompanied by increased VEGF.

Objective

US women exhibit racial disparities in the lifetime risk of diabetes and related outcomes. Identifying heterogeneity in clinical presentation may assist with reducing racial disparities in diabetes outcomes. We identified clinical phenotypes of diabetes and examined their racial and ethnic distribution in US women.

Research design and methods

We conducted cluster analysis based on five factors in US women with diagnosed diabetes assessed in the National Health and Nutrition Examination Surveys 1999–2018 (n = 825). Multinomial logistic regression analysis was performed to identify racial and ethnic differences in the distribution of phenotypes.

Results

We identified four distinct clinical phenotypes. Two phenotypes, mild age-related and severe insulin-deficient diabetes, each included approximately a third of women. Mild insulin-resistant and severe insulin-resistant diabetes phenotypes accounted for 19.9% and 13.7%, respectively. The distribution of clusters did not differ by race and ethnicity.

Conclusions

The prevalence of four clinically distinct diabetes phenotypes identified in US women did not differ by race and ethnicity.

Background

Management of constipation with currently available modern medicines is costly and chances of side effects are high. This limits their clinical usefulness and remain to be solved, and calls for investigations of new and better compounds. The experimental plant, Euclea racemosa L. (E. racemosa L) is among plants, which are used for management of constipation traditionally but its effect is not yet experimentally validated. Therefore, the aim of the present study is to investigate the laxative effects of this plant.

Methods

The laxative effects of aqueous root extracts of E. racemosa L. were evaluated using gastrointestinal motility, laxative activity, and gastrointestinal secretion tests.

Results

In the laxative test, the 200 and 400 mg/kg doses of plant extract showed a significant increase in percent fecal water content. The plant extract also significantly accelerated the charcoal meal in gastrointestinal motility test of loperamide-constipated mice. Moreover, the experimental plant produced significant Gastrointestinal (GI) transit ratio at all doses but failed to produce a significantly higher fluid accumulation except 400 mg/kg doses of extract in gastrointestinal secretion test. The observed effect of the aqueous root extract might be due to the presence of secondary metabolites. The aqueous root extract of E. racemosa L. revealed the presence of terpenes, saponins, flavonoids and phenols when it was subjected to phytochemical screening.

Conclusion

The investigation obtained from this study suggested that E. racemosa L. has a beneficial effect in producing laxative effect and this substantiate the traditional use of the plant for its claimed indication.

Background

Roux-en-Y gastric bypass surgery (RYGB) improves glycemic control in individuals with severe obesity beyond the effects of weight loss alone. To identify potential underlying mechanisms, we asked how equivalent weight loss from RYGB and from chronic caloric restriction impact gut release of the metabolically beneficial cytokine interleukin-22 (Il-22).

Methods

Obese male Zucker fatty rats were randomized into sham-operated (Sham), RYGB, and sham-operated, body weight-matched to RYGB (BWM) groups. Food intake and body weight were measured regularly for 4 weeks. An oral glucose tolerance test (OGTT) was performed on postoperative day 27. Portal vein plasma, systemic plasma, and whole-wall samples from throughout the gut were collected on postoperative day 28. Gut Il-22 mRNA expression was determined by real-time quantitative PCR. Plasma Il-22 levels were determined by enzyme-linked immunosorbant assay (ELISA).

Results

RYGB and BWM rats had lower food intake and body weight as well as superior blood glucose clearing capability compared with Sham rats. RYGB rats also had superior blood glucose clearing capability compared with BWM rats despite having similar body weights and higher food intake. Il-22 mRNA expression was approximately 100-fold higher specifically in the upper jejunum in RYGB rats compared with Sham rats. Il-22 protein was only detectable in portal vein (34.1 ± 9.4 pg/mL) and systemic (46.9 ± 10.5 pg/mL) plasma in RYGB rats. Area under the curve of blood glucose during the OGTT, but not food intake or body weight, negatively correlated with portal vein and systemic plasma Il-22 levels in RYGB rats.

Conclusions

These results suggest that induction of gut Il-22 release might partly account for the weight loss-independent improvements in glycemic control after RYGB, and further support the use of this cytokine for the treatment of metabolic disease.