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Role of natural mTOR inhibitors in treatment of diabetes mellitus

Journal

FUNDAMENTAL & CLINICAL PHARMACOLOGY
Volume 37, Issue 3, Pages 461-479

Publisher

WILEY
DOI: 10.1111/fcp.12851

Keywords

diabetes mellitus; glucose; mTOR; natural products

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Diabetes mellitus is a common and complex problem with significant socio-economic implications. It is caused by defects in insulin secretion or insulin resistance. Chronic hyperglycemia leads to various complications such as nephropathy, retinopathy, and cardiovascular disease. Traditional herbal medicine plays a significant role in diabetes treatment.
Diabetes mellitus is one of the most common and complex problems in today's society and is responsible for many socio-economic problems. Type 1 diabetes is due to a defect in insulin secretion caused by a destruction of pancreatic beta cells. In contrast, the pathogenesis of type 2 diabetes is associated with the development of insulin resistance in the liver and peripheral tissues, a decrease in beta-cell mass, and a defect in insulin secretion. Various factors such as inflammation, stress, obesity, and lifestyle are involved in diabetes. Long-term or chronic increase in glucose in these patients is the leading causes of secondary disorders such as micro- and macro-angiopathy, weakness of the antioxidant defense system, and metabolic disorders and altered lipid profile. The above conditions lead to short-term and long-term complications. These complications cause damage to the physical and physiological function of diverse organs of the body and threaten human health. Late complications of diabetes, including nephropathy, retinopathy, cardiovascular complications, neuropathy, hypertension, and weight gain, are common, and more research has been done on them. Numerous drugs such as meglitinides, biguanides, and thiazolidinedione have been proposed to reduce high blood sugar, but due to the lack of complete cure of this disease with the use of existing drugs, the tendency to use alternative and traditional therapies has increased. In the meantime, the role of herbs with hypoglycemic properties in the treatment of diabetic patients cannot be ignored. The consumption of herbs by people with diabetes has become widespread even in Western countries. The use of herbs could be considered when conventional therapies cannot control the disease, and the patient needs to be prescribed insulin. The mammalian target of rapamycin, mTOR, plays a significant role in regulating cell growth, cellular metabolic status in response to nutrients, many extracellular cues, and growth factors. Impaired insulin secretion can lead to altered mTOR signaling. The mTOR pathway has shown different behaviors depending on the situation. It has been shown that mTOR can regulate the adaptation of beta cells to blood sugar, and chronic inhibition of the mTOR pathway can also induce diabetes. Here, we have reviewed recent findings on the role of mTOR in major metabolic organs, such as the liver, pancreas, brain, and adipose tissue and muscle, and discussed its potential as a diabetes-related drug target.

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