Understanding Type 2 Diabetes
Explain the role of insulin and glucagon in glucose homeostasis., How do defects in insulin secretion and action contribute to the pathogenesis of type 2 diabetes mellitus (T2DM)?, What are the different classes of glucose-lowering medications used to treat T2DM, and how do they target various physiological pathways to improve glycemic control? How does the pathophysiology of T2DM differ from type 1 diabetes, and what are the potential complications associated with chronic hyperglycemia, including neuropathy, retinopathy, and nephropathy?
Role of Insulin and Glucagon in Glucose Homeostasis
Insulin and glucagon are key hormones produced by the pancreas that regulate blood glucose levels:
- Insulin:
- Secreted by beta cells in the islets of Langerhans.
- Promotes glucose uptake by cells, especially in muscle and adipose tissue, and stimulates glycogenesis (the conversion of glucose to glycogen) in the liver.
- Inhibits gluconeogenesis (the production of glucose from non-carbohydrate sources) and lipolysis (the breakdown of fats).
- Glucagon:
- Secreted by alpha cells in the islets of Langerhans.
- Stimulates glycogenolysis (the breakdown of glycogen to glucose) and gluconeogenesis in the liver, increasing blood glucose levels.
- Opposes the actions of insulin, ensuring that blood glucose levels rise when they fall too low.
Defects in Insulin Secretion and Action in Type 2 Diabetes Mellitus (T2DM)
In T2DM, both defects in insulin secretion and insulin action contribute to the disease’s pathogenesis:
- Insulin Resistance:
- Peripheral tissues (muscle, fat) become less responsive to insulin, leading to reduced glucose uptake and increased blood glucose levels.
- Associated with obesity, particularly visceral fat, which releases inflammatory cytokines that further impair insulin signaling.
- Impaired Insulin Secretion:
- Over time, pancreatic beta cells fail to compensate for insulin resistance by producing enough insulin.
- Chronic high demand for insulin can lead to beta-cell dysfunction and eventual apoptosis.
Classes of Glucose-Lowering Medications for T2DM
Several classes of medications are used to treat T2DM, targeting different physiological pathways:
- Biguanides (e.g., Metformin):
- Decrease hepatic glucose production and improve insulin sensitivity. APA