l-Arginine (Arg) is synthesised from glutamine, glutamate, and proline via the intestinal-renal axis in humans and most other mammals (including pigs, sheep and rats). Arg degradation occurs via multiple pathways that are initiated by arginase, nitric-oxide synthase, Arg:glycine amidinotransferase, and Arg decarboxylase. These pathways produce nitric oxide, polyamines, proline, glutamate, creatine, and agmatine with each having enormous biological importance. Arg is also required for the detoxification of ammonia, which is an extremely toxic substance for the central nervous system. There is compelling evidence that Arg regulates interorgan metabolism of energy substrates and the function of multiple organs. The results of both experimental and clinical studies indicate that Arg is a nutritionally essential amino acid (AA) for spermatogenesis, embryonic survival, fetal and neonatal growth, as well as maintenance of vascular tone and hemodynamics. Moreover, a growing body of evidence clearly indicates that dietary supplementation or intravenous administration of Arg is beneficial in improving reproductive, cardiovascular, pulmonary, renal, gastrointestinal, liver and immune functions, as well as facilitating wound healing, enhancing insulin sensitivity, and maintaining tissue integrity. Additionally, Arg or l-citrulline may provide novel and effective therapies for obesity, diabetes, and the metabolic syndrome. The effect of Arg in treating many developmental and health problems is unique among AAs, and offers great promise for improved health and wellbeing of humans and animals.

Arginine metabolism and nutrition in growth, health and disease

Background: This study was aimed to evaluate the protective effects of a novel anti-hyperglycemic “Mcy protein” isolated from the fruits of Momordica cym

Antihyperlipidemic and Biochemical Activities of Mcy Protein in Streptozotocin Induced Diabetic Rats

Ethnopharmacological survey of plants used in the traditional treatment of hypertension and diabetes in south-eastern Morocco (Errachidia province).

https://link.springer.com/content/pdf/10.1007%2Fs13311-017-0585-0.pdf

Anxiety, Depression, and the Microbiome: A Role for Gut Peptides.

Diabetes is usually associated with inflammation. Inflammation contributes to the development of diabetes. Traditional Chinese medicines (TCM) play an important role in lowering blood glucose and controlling inflammation. Many studies show that TCM with hypoglycaemic effects, for example Radix Astragali, Radix Rehmanniae, Radix Trichosanthis, Panax Ginseng, Fructus Schisandrae, Radix Ophiopogonis, Rhizoma Anemarrhenae, Radix Puerariae, Fructus Lycii, Poria, Rhizoma Coptidis, Rhizoma Dioscoreae, Rhizoma Polygonati, Radix Salviae Miltiorrhizae, Radix Glycyrrhizae, Semen Trigonellae, Momordica charantia, Allium sativum, Opuntia stricta, Aloe vera, Cortex Cinnamomi, Rhizoma Curcumae Longae, and so on, have nearly independent anti-inflammatory action. Antihyperglycaemic compounds, for example berberine, puerarin, quercetin, ferulic acid, astragaloside IV, curcumin, epigallocatechin gallate, resveratrol, tetrandrine, glycyrrhizin, emodin and baicalin, used in TCM also have anti-inflammatory effects. These studies suggest that TCM might exert hypoglycaemic effects that are partly mediated by the anti-inflammatory mechanisms. However, small amounts of TCM with potent anti-inflammatory action does not have any hypoglycaemic effect. This indirectly indicates that diabetes may be a low-grade inflammatory disease and potent regulation of inflammatory mediators may not be required. Studies of TCM add new evidences, which indicate that diabetes may be an inflammatory disease and slight or moderate inhibition of inflammation might be useful to prevent the development of diabetes. Through this review, we aim to develop more perspectives to indicate that diabetes may be an inflammatory disease and diverse TCM may share a common antidiabetic property: anti-inflammatory action. Further studies should focus on and validate inflammation-regulating targets of TCM that may be involved in inhibiting the development of diabetes.

Diabetes is an inflammatory disease: evidence from traditional Chinese medicines.

streptozotocin- induced diabetic rats

Modulation of glucagon-like peptide-1 release by berberine: In vivo and in vitro studies

Panax ginseng is one of the most popular herbal remedies. Ginsenosides, major bioactive constituents in P. ginseng, have shown good antidiabetic action, but the precise mechanism was not fully understood. Glucagon-like peptide-1 (GLP1) is considered to be an important incretin that can regulate glucose homeostasis in the gastrointestinal tract after meals. The aim of this study was to investigate whether ginseng total saponins (GTS) exerts its antidiabetic effects via modulating GLP1 release. Ginsenoside Rb1 (Rb1), the most abundant constituent in GTS, was selected to further explore the underlying mechanisms in cultured NCI-H716 cells. Diabetic rats were developed by a combination of high-fat diet and low-dose streptozotocin injection. The diabetic rats orally received GTS (150 or 300 mg/kg) daily for 4 weeks. It was found that GTS treatment significantly ameliorated hyperglycemia and dyslipidemia, accompanied by a significant increase in glucose-induced GLP1 secretion and upregulation of proglucagon gene expression. Data from NCI-H716 cells showed that both GTS and Rb1 promoted GLP1 secretion. It was observed that Rb1 increased the ratio of intracellular ATP to ADP concentration and intracellular Ca 2C concentration. The metabolic inhibitor azide (3 mM), the KATP channel opener diazoxide (340 mM), and the Ca 2C channel blocker nifedipine (20 mM) significantly reversed Rb1-mediated GLP1 secretion. All these results drew a conclusion that ginsenosides stimulated GLP1 secretion both in vivo and in vitro. The antidiabetic effects of ginsenosides may be a result of enhanced GLP1 secretion.

/pdf/increased-glucagon-like-peptide-1-secretion-may-be-involved-4lferabi52.pdf

Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides

Clinical reports have demonstrated that berberine is a potential antidiabetic agent, but the underlying mechanism is unclear. The purpose of this study was to investigate if berberine exerts its hypoglycemic action via inhibiting intestinal disaccharidases using in vivo and in vitro experiments. Streptozotocin-induced diabetic rats received berberine (100 or 200 mg/kg) orally once daily or acarbose (40 mg/kg) orally twice daily for 5 weeks. Disaccharidase activities and sucrase-isomaltase (SI) complex messenger RNA (mRNA) expression in intestinal regions were assessed. The same treatment was operated in normal rats. Sucrose and maltose loading tests were also documented. In addition, Caco-2 cells were cultured in medium containing berberine or berberine plus chelerythrine. Compound C or H-89 for 5 days, disaccharidase activities, and SI complex mRNA levels were measured. The animal experiments showed that berberine significantly decreased the disaccharidase activities and SI complex mRNA expression both in diabetic rats and normal rats. Berberine can also significantly lower postprandial blood glucose levels induced by sucrose or maltose loading in normal rats. The cellular results showed that berberine may suppress disaccharidase activities and downregulate SI complex mRNA expression in a concentration-dependent manner. Only H-89, an inhibitor of protein kinase A (PKA), may reverse the decrease in disaccharidase activities and SI complex mRNA expression induced by berberine. In conclusion, berberine suppresses disaccharidase activities and SI complex mRNA expression with beneficial metabolic effects in diabetic states. The inhibitory effect, at least partly, involves the PKA-dependent pathway.

Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study

Our previous study showed a higher exposure of berberine, palmatine, coptisine, epiberberine and jatrorrhizine in 6-week streptozotocin (STZ)-induced diabetic rats, after oral administration of Coptidis Rhizoma extract. The aim of the present study was to investigate whether the function and expression of intestinal P-glycoprotein (P-GP) was downregulated in STZ-induced diabetic rats and if the impairment of P-GP function and expression contributed to the exposure increase of the five protoberberine alkaloids. Plasma concentration-time profiles of the drugs in the portal vein were obtained after oral administration of Coptidis Rhizoma extract. The effective permeability of the drug across duodenum and ileum were measured using in situ single-pass intestine perfusion. P-GP function in the rat intestine was assessed by measuring the absorption of rhodamine 123 (Rho123). P-GP levels were evaluated using Western blots. It was found that the C(max) and AUC(0-8) values of five alkaloids in the portal vein of diabetic rats were significantly higher than those in the control rats. Diabetic rats also exhibitd a higher level of Rho123 in the portal vein, which showed impairment of P-GP function. A higher effective permeability of the tested drug was found in the duodenum of diabetic rats using in situ single-pass intestine perfusion, indicating that berberine and Rho123 transported more easily across the intestinal barrier of diabetic rats. A lower level of P-GP protein was found in the duodenum, jejunum and ileum of the diabetic rats as compared with age-matched control rats. All these results suggested that the function and expression of P-GP were impaired in the intestine of STZ-induced diabetic rats which, at least partly, contributed to the exposure increase of the five protoberberine alkaloids.

Yun-Li Yu

Papers

streptozotocin- induced diabetic rats

Modulation of glucagon-like peptide-1 release by berberine: In vivo and in vitro studies

Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides

Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study

Increased plasma exposures of five protoberberine alkaloids from Coptidis Rhizoma in streptozotocin-induced diabetic rats: is P-GP involved?