Herbal Therapies for Type 2 Diabetes Mellitus: Chemistry, Biology, and Potential Application of Selected Plants and Compounds
Figure 1
Etiology, development, and current therapies for T2D. (a) Genetic and environmental factors are the main contributors to the development of insulin resistance and impaired glucose tolerance. Under normal glucose tolerance conditions, cells secrete insulin in response to a surge in glucose after a meal. At the initial stage, cells overwork to compensate for the development of insulin resistance. Later on, cells are no longer able to secrete enough insulin to overcome insulin resistance. As a result, glucose tolerance is impaired and the disease progresses from prediabetes to diabetes. Diabetes is characterized as a loss of blood glucose homeostasis, a condition termed hyperglycemia, in the patients. Glucotoxicity, lipotoxicity, ER/oxidative stress, inflammation, and incretin impairment are risk factors for -cell dysfunction. Besides insulin, insulin releasers, insulin sensitizers, GLP-1 analogues/DDP-4 inhibitors, and a-glucosidase inhibitors and Sglt 2 inhibitors are common antidiabetic drugs. (b) Insulin releasers (e.g., sulfonylureas such as glibenclamide and glimepiride) can stimulate pancreatic cells to secrete insulin. Insulin sensitizers (TZDs (e.g., rosiglitazone and pioglitazone) and biguanide (metformin)) reduce insulin resistance in the peripheral tissues. GLP-1 has multiple direct actions on pancreas (insulin and glucagon production) and gastric emptying. Injection of exogenous GLP-1 (e.g., exenatide and liraglutide) or inhibition of endogenous GLP-1 degradation by DPP-4 inhibitors (e.g., sitagliptin, vildagliptin, saxagliptin, and linagliptin) can maintain GLP-1 levels. Inhibitors of -glucosidases (acarbose) and Sglt 2 (e.g., dapagliflozin and empagliflozin) reduce glucose absorption in guts and glucose reabsorption in kidney, respectively. All the drugs can diminish hyperglycemia. *Sglt 2 inhibitors were disproved by the FDA because of a safety issue.
