Antidiabetic Activity (Anti-Hyperglycemic Activity, Anti-Hyperlipidemic Activity)/Agents From Medicinal Plants

Diabetes mellitus (DM) is a chronic disease caused by inherited or acquired deficiency in insulin secretion and by decreased insulin secretion by the organ. Insulin deficiency causes the DM. Synthetic drugs are widely used in the treatment of diabetes, but they have some side effects. The antihyperglycemic and antihyperlipedemic effects of the plants are related to their ability to maintain pancreatic function. Medicinal plants constituents such as glycosides, alkaloids, terpenoids, and flavonoids mitigate DM. B. ciliata inhibits the α-glucosidase and α-amylase. Cinnamon extracts improve insulin receptor function by activating insulin receptor kinase and inhibiting insulin receptor phosphatase, which lead to an increase in insulin sensitivity. Morinda lucida also had the highest antioxidant activity, and it also inhibited the α-glucosidase. Many plants have also been shown to antihyperlipedemic effects. Finally, it can be concluded that medicinal plants have that ability to treat or prevent DM.

Influence of the relative insulin deficiency of the mother on the functional state of the central nervous system of the fetus in the third trimester of pregnancy

85 women from the 28-th to the 40-th week of pregnancy were examined.Nineteen women with impaired glucose tolerance in the third trimester of pregnancy formed the control group. Forty women had gestational diabetes and 26 insulin independent diabetes. The data reveal negative influence of relative insulin insufficiency in expectant mothers on formation of the central neural system of the fetus that is displayed in shortening or even absence of quiet state phase, prolongation of the intermediate state, decrease of motor-cardiac reflex. The intensity of these disturbances depends upon the diabetes type and the rate ofits compensation.

Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model

Adipose tissue (AT) is no longer considered to be responsible for energy storage only but is now recognized as a major endocrine organ that is distributed across different parts of the body and is actively involved in regulatory processes controlling energy homeostasis. Moreover, AT plays a crucial role in the development of metabolic disease such as diabetes. Recent evidence has shown that adipokines have the ability to regulate blood glucose levels and improve metabolic homeostasis. While AT has been studied extensively in the context of type 2 diabetes, less is known about how different AT types are affected by absolute insulin deficiency in type 1 or permanent neonatal diabetes mellitus. Here, we analyzed visceral and subcutaneous AT in a diabetic, insulin-deficient pig model (MIDY) and wild-type (WT) littermate controls by RNA sequencing and quantitative proteomics. Multi-omics analysis indicates a depot-specific dysregulation of crucial metabolic pathways in MIDY AT samples. We identified key proteins involved in glucose uptake and downstream signaling, lipogenesis, lipolysis and β-oxidation to be differentially regulated between visceral and subcutaneous AT in response to insulin deficiency. Proteins related to glycogenolysis, pyruvate metabolism, TCA cycle and lipogenesis were increased in subcutaneous AT, whereas β-oxidation-related proteins were increased in visceral AT from MIDY pigs, pointing at a regionally different metabolic adaptation to master energy stress arising from diminished glucose utilization in MIDY AT. Chronic, absolute insulin deficiency and hyperglycemia revealed fat depot-specific signatures using multi-omics analysis. The generated datasets are a valuable resource for further comparative and translational studies in clinical diabetes research.

Prevalence and phenotypic features of diabetes due to recessive, non-syndromic WFS1 mutations

Objective: Recessive WFS1 mutations are known to cause Wolfram syndrome, a very rare systemic disorder. However, they were also found in non-syndromic diabetes in Han Chinese misdiagnosed with type 1 diabetes, a molecular cause that appears to be considerably more common than the fully expressed syndrome. We aimed to better define the incidence and clinical features of non-syndromic diabetes due to recessive WFS1 mutation. Design: We analyzed the genotype and phenotype of 320 consecutive incident Chinese pediatric diabetic patients diagnosed from 2016 to 2019 to search for non-syndromic diabetic cases due to recessive WFS1 mutation. Methods: A cohort of 105 pancreatic autoantibody-negative patients were recruited for exome sequencing. All patients tested positive for pathogenic diallelic WFS1 mutations were examined for phenotypic features (fundoscopy, audiogram, urine density). Results: We found three cases of non-syndromic diabetes due to recessive WFS1 mutations (incidence = 0.94% (95CI 0.25%-2.7%)). All three cases only had mild diabetes when diagnosed. All patients had well conserved fasting C-peptide when diagnosed but one of them progressed to T1D-like insulin deficiency. In addition, we found a fourth case with previously undetected features of Wolfram syndrome. Conclusions: Non-syndromic diabetes due to WFS1 mutation may be common among Chinese pediatric patients with diabetes. It is important to differentiate it from other MODY subtypes with similar phenotype by molecular diagnosis because of different prognosis and, potentially, therapy.

Determination of autoantibodies in dogs with diabetes mellitus

Background and Aim: The classification of diabetes mellitus (DM) in dogs has been controversial as currently canine insulin-dependent DM is classified together with absolute insulin deficiency, non-insulin-dependent DM, and relative insulin deficiency. Studies on human autoantibodies evaluated in canines with DM, such as anti-glutamic acid decarboxylase (GAD65), anti-islet antigen 2 (IA2), and anti-zinc transporter isoform 8 (ZnT8), have been inconclusive. Thus, this study was designed to establish the serological profile of anti-GAD65, anti-IA2, and anti-ZnT8 antibodies in a group of dogs with and without DM. Materials and Methods: Sixty-one dogs, including 31 patients with DM (with and without insulin treatment) and 30 patients without DM (normal weight and obese), were included for determining autoantibodies using a human enzyme-linked immunosorbent assay (ELISA) detection system for type 1 DM. Results: This study found the presence of anti-IA2 antibodies in 58% of the sample (18/31 patients with DM); however, the presence of anti-GAD65 was not detected, and anti-ZnT8 was found in 3 (9.6%) patients with DM. Conclusion: This study showed a higher positive frequency of anti-IA2 antibodies in a sample of canine with DM, indicating that alterations in the signaling vesicle tyrosine phosphatase 2 lead to lower insulin release and thus to an increase in patients' glycemia. These preliminary results should be taken with caution and corroborated by a canine-specific assay when an ELISA is available for such determination.

PGRMC1 acts as a size-selective cargo receptor to drive ER-phagic clearance of mutant prohormones

The reticulon-3 (RTN3)-driven targeting complex promotes clearance of misfolded prohormones from the endoplasmic reticulum (ER) for lysosomal destruction by ER-phagy. Because RTN3 resides in the cytosolic leaflet of the ER bilayer, the mechanism of selecting misfolded prohormones as ER-phagy cargo on the luminal side of the ER membrane remains unknown. Here we identify the ER transmembrane protein PGRMC1 as an RTN3-binding partner. Via its luminal domain, PGRMC1 captures misfolded prohormones, targeting them for RTN3-dependent ER-phagy. PGRMC1 selects cargos that are smaller than the large size of other reported ER-phagy substrates. Cargos for PGRMC1 include mutant proinsulins that block secretion of wildtype proinsulin through dominant-negative interactions within the ER, causing insulin-deficiency. Chemical perturbation of PGRMC1 partially restores WT insulin storage by preventing ER-phagic degradation of WT and mutant proinsulin. Thus, PGRMC1 acts as a size-selective cargo receptor during RTN3-dependent ER-phagy, and is a potential therapeutic target for diabetes.

Hypoglycemic Activities of Ethanolic Leave Extract of Acalypha Wilkesiana in Streptozotocin-Induced Diabetic Wistar Rats

Diabetes is a rampant metabolic disorder of insulin deficiency or resistance. In support of the alternative therapy quest, this study investigates the antidiabetic actions of ethanolic leave extract of Acalypha wilkesiana (A. wilkesiana) in diabetic rats. The study was conducted in 3 phases using streptozotocin (50mg/kg) induced diabetic adult Wistar rats. In phase one, 18 diabetic rats were divided into 3 groups (n=6) and treated with distilled-water (10ml/kg), glimepiride (0.1mg/kg) and ethanolic leave extract of A. wilkesiana (250mg/kg) respectively. On separate 18 diabetic rats (phase two), 5% glucose (10ml/kg) was administered after treatments as in phase one. Blood glucose was measured at 0 and 30-minute intervals for 180 minutes in both phases. On another 18 diabetic rats (phase three), similar treatments were given daily for 14 days. Blood glucose was measured at day 0, 3 days after induction, 3, 7, 10, and 14 days treatments. ANOVA was carried out with p <0.05 as significant. The results showed progressively hypoglycemic actions significant from the 90th minute with glimepiride (285.17±12.09mg/dl) and the 120th minute with the extract (279.83±14.88mg/dl) through 180 minutes compared to control in 1st-phase. There was a significant obliterating effect on glucose-induced hyperglycemia in a time-dependent manner at 90th through 180th minutes after glucose loading in glimepiride and extract-treated groups compared to control (2nd phase). Streptozotocin-induced decreased body weight was improved in glimepiride and extract-treated groups by days 7 and 14 and there was a significant steady duration-dependent decrease in blood glucose from the 3rd to 14th day of treatments compared to control. The findings suggest that ethanolic leaves extract of A. wilkesiana possesses antidiabetic action probably through stimulation of pancreatic β-cells or improves insulin action.

Studies of the Anti-Diabetic Mechanism of Pueraria lobata Based on Metabolomics and Network Pharmacology

Diabetes mellitus (DM), as a chronic disease caused by insulin deficiency or using obstacles, is gradually becoming a principal worldwide health problem. Pueraria lobata is one of the traditional Chinese medicinal and edible plants, playing roles in improving the cardiovascular system, lowering blood sugar, anti-inflammation, anti-oxidation, and so on. Studies on the hypoglycemic effects of Pueraria lobata were also frequently reported. To determine the active ingredients and related targets of Pueraria lobata for DM, 256 metabolites were identified by LC/MS non targeted metabonomics, and 19 active ingredients interacting with 51 DM-related targets were screened. The results showed that puerarin, quercetin, genistein, daidzein, and other active ingredients in Pueraria lobata could participate in the AGE-RAGE signaling pathway, insulin resistance, HIF-1 signaling pathway, FoxO signaling pathway, and MAPK signaling pathway by acting on VEGFA, INS, INSR, IL-6, TNF and AKT1, and may regulate type 2 diabetes, inflammation, atherosis and diabetes complications, such as diabetic retinopathy, diabetic nephropathy, and diabetic cardiomyopathy.