Studies have shown that targeting xanthine oxidase (XO) can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia. This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato (diacylated AF-PSPs) on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet. The body weight, organ index, serum biochemical indexes, and liver antioxidant indexes of mice were measured, and the kidneys were observed in pathological sections. The relative expression levels of messenger RNAs (mRNAs) of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain (qPCR) reaction technique, and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry (IHC) technique. Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice, and that this effect might be related to the regulation of liver XO activity, lipid accumulation, and relevant renal transporters. Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder, liver lipid accumulation, and liver oxidative stress, thereby enhancing insulin utilization and sensitivity, lowering blood sugar, and reducing hyperglycemia in mice. Also, diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism, and reduced kidney injury and inflammation. This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid (UA) by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.
Mice ; Animals ; Hyperuricemia/drug therapy* ; Diet, High-Fat/adverse effects* ; Anthocyanins/chemistry* ; Ipomoea batatas/chemistry* ; Fructose/adverse effects* ; Hyperglycemia/drug therapy* ; Lipids

Diabetes mellitus is a chronic disease, typified by hyperglycemia resulting from failures in complex multifactorial metabolic functions, that requires life-long medication. Prolonged uncontrolled hyperglycemia leads to micro- and macro-vascular complications. Although antidiabetic drugs are prescribed as the first-line treatment, many of them lose efficacy over time or have severe side effects. There is a lack of in-depth study on the patents filed concerning the use of natural compounds to manage diabetes. Thus, this patent analysis provides a comprehensive report on the antidiabetic therapeutic activity of 6 phytocompounds when taken alone or in combinations. Four patent databases were searched, and 17,649 patents filed between 2001 and 2021 were retrieved. Of these, 139 patents for antidiabetic therapeutic aids that included berberine, curcumin, gingerol, gymnemic acid, gymnemagenin and mangiferin were analyzed. The results showed that these compounds alone or in combinations, targeting acetyl-coenzyme A carboxylase 2, serine/threonine protein kinase, α-amylase, α-glucosidase, lipooxygenase, phosphorylase, peroxisome proliferator-activated receptor-γ (PPARγ), protein tyrosine phosphatase 1B, PPARγ co-activator-1α, phosphoinositide 3-kinase and protein phosphatase 1 regulatory subunit 3C, could regulate glucose metabolism which are validated by pharmacological rationale. Synergism, or combination therapy, including different phytocompounds and plant extracts, has been studied extensively and found effective, whereas the efficacy of commercial drugs in combination with phytocompounds has not been studied in detail. Curcumin, gymnemic acid and mangiferin were found to be effective against diabetes-related complications. Please cite this article as: DasNandy A, Virge R, Hegde HV, Chattopadhyay D. A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications. J Integr Med. 2023; 21(3): 226-235.
Humans ; PPAR gamma/metabolism* ; Curcumin/therapeutic use* ; Phosphatidylinositol 3-Kinases ; Diabetes Mellitus/drug therapy* ; Hypoglycemic Agents/pharmacology* ; Hyperglycemia/drug therapy* ; Glucose

Humans ; Neutrophils ; Retrospective Studies ; Leukocyte Count ; Hyperglycemia/drug therapy* ; Insulins ; Insulin/therapeutic use*

Type 2 diabetes mellitus is a progressive process. With the course of the disease progress, microvascular and macrovascular complications always happen. Thrombotic events caused by macrovascular complications, including coronary heart diseases and cerebrovascular diseases, are the main fatal factor for the patients with type 2 diabetes. Endothelial dysfunction, coagulative activation, impaired fibrinolysis, together with hyper-reactive platelets contribute to the diabetic prothrombotic state, which is strongly related to the macrovascular complications. In particular, the hyper-reactive platelets play a fundamental role among them. Type 2 diabetes is characterized by several metabolic dysfunctions such as hyperglycemia, insulin resistance and shortage, oxidative stress, systemic inflammation, obesity, and dyslipidemia. These metabolic dysfunctions work together to promote the formation of hyper-reactive platelets, which are distinctive in type 2 diabetes. The regular antiplatelet drugs, like aspirin, show limited inhibitory effect on them. Hence, studying the mechanism behind the hyper-reactive platelets could provide a brand-new view on the prevention of macrovascular complications and cardiovascular events in type 2 diabetes.
Blood Platelets ; Diabetes Mellitus, Type 2/drug therapy* ; Humans ; Hyperglycemia/complications* ; Insulin Resistance ; Obesity/complications*

Animals ; Diabetes Mellitus, Experimental/drug therapy* ; Fibrosis/prevention & control* ; Hyperglycemia/prevention & control* ; Hypoglycemic Agents/pharmacology* ; Inflammation/prevention & control* ; Male ; Rats ; Rats, Sprague-Dawley ; Stilbenes/pharmacology*

Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide (WIP) was isolated and identified from the sclerotium of Poria cocos, a widely used Traditional Chinese Medicine. WIP was confirmed to be a (1-3)-β-D-glucan with an average Mw of 4.486 × 10 Da by NMR and SEC-RI-MALLS analyses. Furthermore, oral treatment with WIP from P. cocos significantly improved glucose and lipid metabolism and alleviated hepatic steatosis in ob/ob mice. 16S DNA sequencing analysis of cecum content from WIP-treated mice indicated the increase of butyrate-producing bacteria Lachnospiracea, Clostridium. It was also observed that WIP treatment elevated the level of butyrate in gut, improved the gut mucosal integrity and activated the intestinal PPAR-γ pathway. Fecal transplantation experiments definitely confirmed the causative role of gut microbiota in mediating the benefits of WIP. It is the first report that the water insoluble polysaccharide from the sclerotium of P. cocos modulates gut microbiota to improve hyperglycemia and hyperlipidemia. Thereby, WIP from P. cocos, as a prebiotic, has the potential for the prevention or cure of metabolic diseases and may elucidate new mechanism for the efficacies of this traditional herbal medicine on the regulation of lipid and glucose metabolism.
Animals ; Bacteria ; classification ; genetics ; isolation & purification ; metabolism ; Butyrates ; metabolism ; Fatty Liver ; drug therapy ; Fungal Polysaccharides ; chemistry ; pharmacology ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; genetics ; Hyperglycemia ; drug therapy ; Hyperlipidemias ; drug therapy ; Intestines ; drug effects ; microbiology ; Male ; Metabolic Syndrome ; drug therapy ; Mice ; Mice, Obese ; Prebiotics ; Wolfiporia ; chemistry

BACKGROUND: We evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin. METHODS: A total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24. RESULTS: The add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P<0.001 vs. baseline) decrease in glycosylated hemoglobin (HbA1c) at week 16, while changes in HbA1c were insignificant in the Met+Sita group (−0.09%±0.10%, P=0.113). After 8 weeks of triple combination therapy, HbA1c levels were comparable between Met+Sita and Met+Sita+Acarb group (7.66%±0.13% vs. 7.47%±0.12%, P=0.321). Acarbose add-on therapy demonstrated suppressed glucagon secretion (area under the curve of glucagon, 4,726.17±415.80 ng·min/L vs. 3,314.38±191.63 ng·min/L, P=0.004) in the absence of excess insulin secretion during the meal tolerance tests at week 16 versus baseline. The incidence of adverse or serious adverse events was similar between two groups. CONCLUSION: In conclusion, a 16-week acarbose add-on therapy to metformin and sitagliptin, effectively lowered HbA1c without significant adverse events. Acarbose might be a good choice as a third-line therapy in addition to metformin and sitagliptin in Korean subjects with T2DM who have predominant postprandial hyperglycemia and a high carbohydrate intake.
Acarbose ; Diabetes Mellitus, Type 2 ; Drug Therapy, Combination ; Glucagon ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia ; Incidence ; Insulin ; Korea ; Meals ; Metformin ; Sitagliptin Phosphate

Diabetes is a widespread, rapidly increasing metabolic disease that is driven by hyperglycemia. Early glycemic control is of primary importance to avoid vascular complications including development of retinal disorders leading to blindness, end-stage renal disease, and accelerated atherosclerosis with a higher risk of myocardial infarction, stroke and limb amputations. Even after hyperglycemia has been brought under control, "metabolic memory," a cluster of irreversible metabolic changes that allow diabetes to progress, may persist depending on the duration of hyperglycemia. Manipulation of bile acid (BA) receptors and the BA pool have been shown to be useful in establishing glycemic control in diabetes due to their ability to regulate energy metabolism by binding and activating nuclear transcription factors such as farnesoid X receptor (FXR) in liver and intestine as well as the G-protein coupled receptor, TGR5, in enteroendocrine cells and pancreatic β-cells. The downstream targets of BA activated FXR, FGF15/21, are also important for glucose/insulin homeostasis. In this review we will discuss the effect of BAs on glucose and lipid metabolism and explore recent research on establishing glycemic control in diabetes through the manipulation of BAs and their receptors in the liver, intestine and pancreas, alteration of the enterohepatic circulation, bariatric surgery and alignment of circadian rhythms.
Animals ; Bile Acids and Salts ; blood ; metabolism ; Blood Glucose ; drug effects ; metabolism ; Circadian Rhythm ; Diabetes Mellitus ; blood ; drug therapy ; metabolism ; Energy Metabolism ; Homeostasis ; Humans ; Hyperglycemia ; metabolism ; physiopathology ; Hypoglycemic Agents ; therapeutic use ; Intestinal Mucosa ; metabolism ; Intestines ; drug effects ; Lipid Metabolism ; Liver ; drug effects ; metabolism ; Receptors, Cytoplasmic and Nuclear ; metabolism ; Receptors, G-Protein-Coupled ; metabolism ; Signal Transduction

Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output. Screening strategies for this condition include random glucose testing, hemoglobin A1c testing, oral glucose loading, and fasting plasma glucose screens. The management of hyperglycemia starts with insulin or sulfonylurea, depending on the type, dose, and delivery of the glucocorticoid formulation. Mammalian target of rapamycin (mTOR) inhibitors are associated with a high incidence of hyperglycemia, ranging from 13% to 50%. Immunotherapy, such as anti-programmed death 1 (PD-1) antibody treatment, induces hyperglycemia with a prevalence of 0.1%. The proposed mechanism of immunotherapy-induced hyperglycemia is an autoimmune process (insulitis). Withdrawal of the PD-1 inhibitor is the primary treatment for severe hyperglycemia. The efficacy of glucocorticoid therapy is not fully established and the decision to resume PD-1 inhibitor therapy depends on the severity of the hyperglycemia. Diabetic patients should achieve optimized glycemic control before initiating treatment, and glucose levels should be monitored periodically in patients initiating mTOR inhibitor or PD-1 inhibitor therapy. With regard to hyperglycemia caused by anti-cancer therapy, frequent monitoring and proper management are important for promoting the efficacy of anti-cancer therapy and improving patients' quality of life.
Blood Glucose ; Drug Therapy ; Fasting ; Glucocorticoids ; Glucose ; Hematologic Neoplasms ; Humans ; Hyperglycemia* ; Immunotherapy ; Incidence ; Insulin ; Insulin Resistance ; Mass Screening ; Prevalence ; Quality of Life ; Sirolimus ; Whole-Body Irradiation

OBJECTIVETo investigate the effects of hydro-alcoholic extract of Launaea acanthodes, a blood glucose lowering plant in folk medicine of Iran, on the structure of seminiferous tubules and serum gonadotropin and testosterone levels in hyperglycemic rats.

METHODSTwenty-four Wistar rats were randomly allocated into 4 groups (n=6): control, streptozotocin (STZ), STZ + insulin [STZ + Ins, 5 IU/(kg•day)], and STZ + Launaea acanthodes extract [STZ + Ext, 150 mg/(kg•day)]. Blood samples were collected at the 2nd and 4th weeks for detection of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) with enzyme-linked immuno sorbent assay (ELISA), and the right testes of rats were removed at the 7th week for the evaluation of diameter and wall thickness of seminiferous tubules and number of Leydig cells using unbiased stereological techniques.

RESULTSIn comparison with the control group, at the 2nd week FSH (0.45 vs 0.03, 0.02, 0.02 IU/L in STZ, STZ + Ins and STZ + Ext groups, respectively) and LH (1.02 vs 0.37, 0.2, 0.29 IU/L) showed significant decreases (all P<0.05) and testosterone (4.2 vs 8.37, 7.78, 11.8 ng/mL) showed a remarkable increase (all P<0.05). The levels of these hormones became closer in the STZ + Ext and the STZ + Ins groups to the control at the 4th week. A significant decrease in diameter and wall thickness of seminiferous tubules and number of Leydig cells were observed in the STZ group as compared with the control (P<0.01).

CONCLUSIONSAdministration of Launaea extract demonstrated a beneficial impact on the protection of testis from pathogenic and degenerative effects of hyperglycemia which may be partly due to its potential antioxidative effects.

Animals ; Asteraceae ; chemistry ; Blood Glucose ; metabolism ; Cell Count ; Cholesterol ; blood ; Ethanol ; chemistry ; Gonadotropins ; blood ; Hyperglycemia ; blood ; drug therapy ; pathology ; Insulin ; blood ; Leydig Cells ; drug effects ; pathology ; Lipoproteins ; blood ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Seminiferous Tubules ; drug effects ; pathology ; Testosterone ; blood ; Triglycerides ; blood ; Water ; chemistry