An Update on the Molecular and Cellular Basis of Pharmacotherapy in Type 2 Diabetes Mellitus

Abstract

Diabetes mellitus (DM) is a chronic illness with an increasing global prevalence. More than 537 million cases of diabetes were reported worldwide in 2021, and the number is steadily increasing. The worldwide number of people suffering from DM is projected to reach 783 million in 2045. In 2021 alone, more than USD 966 billion was spent on the management of DM. Reduced physical activity due to urbanization is believed to be the major cause of the increase in the incidence of the disease, as it is associated with higher rates of obesity. Diabetes poses a risk for chronic complications such as nephropathy, angiopathy, neuropathy and retinopathy. Hence, the successful management of blood glucose is the cornerstone of DM therapy. The effective management of the hyperglycemia associated with type 2 diabetes includes physical exercise, diet and therapeutic interventions (insulin, biguanides, second generation sulfonylureas, glucagon-like peptide 1 agonists, dipeptidyl-peptidase 4 inhibitors, thiazolidinediones, amylin mimetics, meglitinides, α-glucosidase inhibitors, sodium-glucose cotransporter-2 inhibitors and bile acid sequestrants). The optimal and timely treatment of DM improves the quality of life and reduces the severe burden of the disease for patients. Genetic testing, examining the roles of different genes involved in the pathogenesis of DM, may also help to achieve optimal DM management in the future by reducing the incidence of DM and by enhancing the use of individualized treatment regimens.

The Anti-Diabetic Potential of Baicalin: Evidence from Rodent Studies

“…This sequence of events triggers insulin exocytosis. Along with glucose, the gut-derived incretin hormones, islet-derived adenosine, and the nervous system (secreting adrenaline and acetylcholine) have a relevant modulatory function on insulin secretion [ 34 , 35 , 36 , 37 , 38 , 39 ]. However, in type 1 diabetes, the insulin-secretory function of β-cells markedly deteriorates, leading to insulin deficiency and the resulting hyperglycemia.…”

“…Sustained hyperglycemia is well known to largely contribute to the progressive failure of cells and organs, including insulin-secreting cells, and is one of the major causative factors of diabetic complications. On the other hand, maintaining blood glucose levels in the physiological range (euglycemia) limits the progression of diabetes and associated complications [ 18 , 19 , 39 ]. Such action is well documented for numerous natural, plant-derived compounds [ 33 , 40 , 41 ], including baicalin.…”

Diagnosis and Non-Invasive Treatment of Obesity in Adults with Type 2 Diabetes Mellitus: A Review of Guidelines

“…As emphasized by Mahgoub et al, insulin resistance has a much broader and multifactorial background [ 28 ]. Not only obesity but also smoking, inadequate physical activity, and excessive consumption of alcoholic beverages are key factors contributing to insulin resistance [ 28 ].…”

“…As emphasized by Mahgoub et al, insulin resistance has a much broader and multifactorial background [ 28 ]. Not only obesity but also smoking, inadequate physical activity, and excessive consumption of alcoholic beverages are key factors contributing to insulin resistance [ 28 ]. All these processes affect the ability of insulin-dependent tissues, mainly the liver, adipose tissue, and skeletal muscle, to metabolize glucose.…”

“…All these processes affect the ability of insulin-dependent tissues, mainly the liver, adipose tissue, and skeletal muscle, to metabolize glucose. The paramount postulated mechanism of the development of insulin resistance is the reduced phosphorylation response of IRS-1 and IRS-2 (insulin receptor substrate-1 and -2) [ 28 , 29 , 30 , 31 ]. This, in turn, leads to further down-regulation of on-cell membranes in insulin-dependent tissues, followed by reduced glucose uptake by these tissues and subsequent hyperglycemia.…”