Berberine Decreases Intestinal GLUT2 Translocation and Reduces Intestinal Glucose Absorption in Mice

Postprandial hyperglycemia is an important causative factor of type 2 diabetes mellitus, and permanent localization of intestinal GLUT2 in the brush border membrane is an important reason of postprandial hyperglycemia. Berberine, a small molecule derived from Coptidis rhizome, has been found to be potent at lowering blood glucose, but how berberine lowers postprandial blood glucose is still elusive. Here, we investigated the effect of berberine on intestinal glucose transporter 2 (GLUT2) translocation and intestinal glucose absorption in type 2 diabetes mouse model. Type 2 diabetes was induced by feeding of a high-fat diet and injection of streptozotocin and diabetic mice were treated with berberine for 6 weeks. The effects of berberine on intestinal glucose transport and GLUT2 translocation were accessed in isolated intestines and intestinal epithelial cells (IEC-6), respectively. We found that berberine treatment improved glucose tolerance and systemic insulin sensitivity in diabetic mice. Furthermore, berberine decreased intestinal glucose transport and inhibited GLUT2 translocation from cytoplasm to brush border membrane in intestinal epithelial cells. Mechanistically, berberine inhibited intestinal insulin-like growth factor 1 (IGF-1R) phosphorylation and thus reduced localization of PLC-β2 in the membrane, leading to decreased GLUT2 translocation. These results suggest that berberine reduces intestinal glucose absorption through inhibiting IGF-1R-PLC-β2-GLUT2 signal pathway.

Herbal Infusions as a Valuable Functional Food

Herbal infusions are an underestimated and easy to intake a source of biologically active natural compounds (polyphenols), which, in the dissolved form, are more easily absorbed. Therefore, this study aimed to assess the potential of herbal infusions as a functional food to reduce postprandial hyperglycemia (inhibition of α-amylase and α-glucosidase) and to reduce the effects of increased blood glucose level (antioxidant effect-DPPH, CUPRAC, and Fe2+ chelating assays, as well as anti-inflammatory activity-inhibition of collagenase). We showed that polyphenols are present in the examined aqueous herbal infusions (including chlorogenic and gallic acids). Subsequently, our research has shown that herbal infusions containing cinnamon bark, mulberry leaves, and blackberry fruits most strongly inhibit glucose release from complex carbohydrates, and that all herbal infusions can, to different degrees, reduce the effects of elevated blood sugar. In conclusion, infusions prepared from herbal blends could be recommended to prevent type II diabetes.

Relationship between heart rate variability, low grade inflammation and glycated hemoglobin. A sugary sweet story

Background Low grade inflammation (LGI) is significantly associated with microvascular complications in diabetes mellitus (DM). Reduced and impaired Heart rate variability (HRV) is a strong marker of autonomic dysfunction and neuropathy and strongly associated with microvascular disease in DM. New studies and observations indicate that the diabetic neuropathic process starts early during pre-diabetes. On the other hand, HRV and LGI are closely interrelated. Our aim was to evaluate whether LGI or hyperglycemia (i.e. high HbA1c) is associated with the autonomic dysfunction or reduced HRV among people with diabetes and pre-diabetes. Methods and materials This study is based on The Copenhagen Holter Study, in which 678 community dwelling subjects aged 55 – 75 years who were free of previous cardiovascular disease, except from well controlled hypertension, and who underwent a 48-hours Holter recording. Analysis of HRV including night-time HRV were available for 653 participants and this population included 133 people with well-controlled and newly recognized T2DM (mean HbA1c 55 mmol/mol (7.2%)) and 386 people with pre-diabetes defined as HbA1c between 39 mmol/mol (5.7%) and 47 mmol/mol (6.4%). We selected high-sensitive CRP, as markers of LGI. As measures of HRV we used the standard deviation of normal-to-normal (N-N) beats (SDNN), the root mean square of N-N beats (RMSSD) which has been acknowledged to be best linked to vagal parasympathetic tone, and the mean time between N-N complexes (meanNN) which represents the average 24-hour heart rate (60.000/meanNN = average 24-hour HR in beats/min) Results Measures of HRV were associated with HgbA1c among both people with T2DM and pre-diabetes. Among people with pre-diabetes HbA1c was inversely associated with 24-hour RMSSD (r=−0.11, p=0.03) and night-time SDNN (r=−0,13, p>0.01), while among T2DM HgbA1c was only associated with 24-hour RMSSD (r=−0.21, p=0.02). These association stayed significant when adjusted for sex, age, BMI, smoking, HOMA-ir, hs-CRP and systolic blood pressure in multiple linear regression (Table 1). LGI was only associated with HRV in diabetes. HbA1c was not associated with any measures of HRV or LGI among people with normal glucose metabolism. Conclusion HRV is closely and inversely associated with HbA1c in both diabetes and prediabetes, but only in diabetes LGI is associated with HRV. This indicates that the process of autonomic dysfunction/neuropathy starts at an early phase during pre-diabetes and probably provoked by postprandial hyperglycemia, while in diabetes both HbA1c and LGI are associated with HRV showing that LGI is activated later in the disease process probably provoked by long-term postprandial hyperglycemia, indicating treatment of hyperglycemia and postprandial hyperglycemia in the prediabetes state may be helpful. FUNDunding Acknowledgement Type of funding sources: None.

Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model

Periodontal infection induces systemic inflammation; therefore, aggravating diabetes. Orally administered periodontal pathogens may directly alter the gut microbiota. We orally treated obese db/db diabetes mice using Porphyromonas gingivalis (Pg). We screened for Pg-specific peptides in the intestinal fecal specimens and examined whether Pg localization influenced the intestinal microbiota profile, in turn altering the levels of the gut metabolites. We evaluated whether the deterioration in fasting hyperglycemia was related to the changes in the intrahepatic glucose metabolism, using proteome and metabolome analyses. Oral Pg treatment aggravated both fasting and postprandial hyperglycemia (P < 0.05), with a significant (P < 0.01) increase in dental alveolar bone resorption. Pg-specific peptides were identified in fecal specimens following oral Pg treatment. The intestinal Pg profoundly altered the gut microbiome profiles at the phylum, family, and genus levels; Prevotella exhibited the largest increase in abundance. In addition, Pg-treatment significantly altered intestinal metabolite levels. Fasting hyperglycemia was associated with the increase in the levels of gluconeogenesis-related enzymes and metabolites without changes in the expression of proinflammatory cytokines and insulin resistance. Oral Pg administration induced gut microbiota changes, leading to entero-hepatic metabolic derangements, thus aggravating hyperglycemia in an obese type 2 diabetes mouse model.

Impact of Lifestyle Behaviors on Postprandial Hyperglycemia during Continuous Glucose Monitoring in Adult Males with Overweight/Obesity but without Diabetes

Data regarding hyperglycemia-related factors were scarce in people without diabetes. Fifty males (age 50–65 years) with overweight/obesity but without diagnosis of diabetes were recruited. After excluding participants with the 2 h plasma glucose value during a 75 g oral glucose tolerance test ≥200 mg/dL, continuous glucose monitoring (CGM) was performed for 6 days. Subjects with ≥1800 CGM readings were included (n = 36). The CGM indices of hyperglycemia were significantly associated with disposition index and snacking frequency. In receiver-operating characteristic analysis for predicting the maximal CGM glucose ≥200 mg/dL, the area under curves of disposition index, snacking frequency, and minimal daily step counts during the study were 0.69, 0.63, and 0.68, whereas the cutoff values were 1.57, once daily, and 2499 steps, respectively. After adjustments, the lower disposition index (≤1.57), higher snacking frequency (≥1 per day), and lower minimal step (≤2499 steps per day) categories conferred 14.5, 14.5, and 6.6-fold increased probabilities for having the maximum level ≥ 200 mg/dL, respectively. In addition, the snacking habits were significantly associated with insulin resistance and compensatory hyperinsulinemia. In conclusion, in middle aged males with overweight/obesity but without diabetes, snacking and physical inactivity serve as the major drivers of postprandial hyperglycemia independently of β-cell function.

Satisfactory Rapid Response to Xultophy Associated with Meal Tolerance Test (MTT) by Carbohydrate Loading

The case is a 69-year-old male patient with Type 2 Diabetes Mellitus (T2DM) for 21 years. His diabetic control was not so satisfactory, and his HbA1c value increased in spring 2021. Then, he started Xultophy (IDegLira), which includes a fixed ratio of two agents of basal degludec and liraglutide. Just after providing Xultophy, the daily profile of blood glucose decreased from 179-400 mg/dL to 112-171 mg/dL, with remarkable clinical efficacy. He usually takes 80g of carbohydrates in breakfast, and the meal tolerance test (MTT) was challenged. As carbohydrate loading was given 100-75-50-0%, postprandial hyperglycemia at 60-min showed 277-219-159-133 mg/dL, respectively.

A Review on Nepalese Medicinal Plants Used Traditionally as Alpha-Amylase and Alpha-Glucosidase Inhibitors Against Diabetes Mellitus

Background: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia in which the blood sugar levels are increased. Nepalese medicinal plants are being used traditionally since long back in the treatment of diabetes. These plants have provided a broad research area in modern medicine development due to their potency to inhibit digestive enzymes. The isolated compounds and crude extract of these plants exhibited the property of inhibiting the digestive enzymes (α-amylase and α-glucosidase). Objective: This review's primary purpose is to explore the inhibitory activity of Nepal's medicinal plants against the digestive enzymes (α-amylase and α-glucosidase) as a practical approach to control type-2 diabetes mellitus (T2DM). Twenty Nepalese medicinal plants belonging to 19 families and compounds isolated from them possessing potent inhibitory activity against digestive enzymes and are responsible for managing postprandial hyperglycemia are reviewed under this article. Methods: The scientific evidence of the tabulated medicinal plants' function in managing postprandial hyperglycemia through inhibition of digestive enzymes (α-amylase and α-glucosidase) was carefully investigated online. As a result, searches in PubMed, Research Gate, and Google Scholar were conducted. All of the data from the various sources have been organized in a structured manner. Result and Conclusion: From the database available, twenty plants with their crude extract and some isolated compounds and their IC50 values are tabulated. Thus, these compounds could be vital components in drug design with fewer side effects and could be a replaceable agent to conquer diabetes threats.