1) Diabetes mellitus is a disorder characterized by hyperglycemia.
Gluconeogenesis is the process by which the liver produces glucose from non-carbohydrate sources such as amino acids and fats. In people with type 2 diabetes, gluconeogenesis can contribute to elevated blood sugar levels, which is a hallmark of the disease. Insulin resistance means that the body's cells do not respond to insulin as effectively as they should, and therefore do not take up glucose from the bloodstream as readily. This leads to elevated blood glucose levels, which can stimulate gluconeogenesis in the liver.
Diabetic ketoacidosis (DKA) is a serious complication of diabetes that occurs when the body produces high levels of ketones (a type of acid) due to a lack of insulin in the body. It is most commonly seen in people with type 1 diabetes, but can also occur in people with type 2 diabetes.
Fasting blood glucose is a test that measures the amount of glucose in the blood after a period of fasting, usually overnight. Random blood glucose is a test that measures the amount of glucose in the blood at any given time. HbA1c is a measure of the average blood glucose levels over the past 2-3 months.
Oral glucose tolerance test (OGTT) may be used to diagnose and monitor diabetes mellitus.
Insulin is not used for the diagnosis of diabetes.
Explanation: According to the American Diabetes Association (ADA), a diagnosis of diabetes requires two abnormal serum glucose measurements taken on separate occasions. For fasting blood glucose, a level of 126 mg/dL or higher is diagnostic of diabetes. For random blood glucose, a level of 200 mg/dL or higher with symptoms of hyperglycemia is diagnostic of diabetes. And for HbA1c, a level of 6.5% or higher is diagnostic of diabetes.
- Insulin auto-antibodies (IAA)
- Glutamic acid decarboxylase antibodies (GADA)
- Zinc transporter 8 antibodies (ZnT8A)
The presence of these auto-antibodies can be detected through blood tests, and their presence is a strong indication of type 1 diabetes. However, not all people with type 1 diabetes will have detectable auto-antibodies, and the absence of auto-antibodies does not rule out a diagnosis of type 1 diabetes.
Prediabetes is diagnosed by measuring fasting blood glucose levels or glucose levels after an oral glucose tolerance test (OGTT). According to the American Diabetes Association (ADA), a fasting blood glucose level between 100-125 mg/dL or a glucose level between 140-199 mg/dL two hours after an OGTT is diagnostic of prediabetes. An HbA1c level between 5.7-6.4% is also diagnostic of prediabetes.
- Biguanides: Examples include metformin, which works by reducing glucose production in the liver and improving insulin sensitivity.
- Sulfonylureas: Examples include glipizide, glyburide, and glimepiride, which work by stimulating the pancreas to produce more insulin.
- Meglitinides: Examples include repaglinide and nateglinide, which work similarly to sulfonylureas but have a shorter duration of action.
- DPP-4 inhibitors: Examples include sitagliptin and linagliptin, which work by increasing the levels of a hormone called incretin, which stimulates insulin production.
- SGLT2 inhibitors: Examples include canagliflozin and dapagliflozin, which work by blocking the reabsorption of glucose in the kidneys, leading to increased glucose excretion in the urine.
- GLP-1 receptor agonists: Examples include exenatide and liraglutide, which work by increasing insulin production and reducing glucose production in the liver, as well as slowing the absorption of glucose from the intestines.
- Decreases hepatic glucose production: Metformin works by reducing the amount of glucose produced by the liver. It inhibits gluconeogenesis (the production of glucose from non-carbohydrate sources) and glycogenolysis (the breakdown of stored glucose).
- Improves insulin sensitivity: Metformin enhances the body's response to insulin, making it easier for the body to use glucose for energy. It increases the uptake of glucose into muscle cells and reduces insulin resistance.
- Decreases intestinal glucose absorption: Metformin can reduce the amount of glucose absorbed from the intestines by inhibiting the activity of an enzyme called alpha-glucosidase, which breaks down complex carbohydrates into glucose.
- Reduces appetite: Metformin has been shown to reduce appetite and promote weight loss in some people, although the exact mechanism is not fully understood.
Overall, the pharmacological effects of metformin help to lower blood glucose levels and improve insulin sensitivity in people with type 2 diabetes.
- Bind to ATP-sensitive potassium channels: Sulfonylureas bind to ATP-sensitive potassium channels on the surface of the beta cells in the pancreas. These channels normally help to regulate the release of insulin by opening in response to high blood glucose levels.
- Stimulate insulin secretion: By binding to the ATP-sensitive potassium channels, sulfonylureas prevent potassium ions from leaving the beta cells, which causes the cells to depolarize and release insulin.
- Increase insulin sensitivity: Sulfonylureas can also increase the sensitivity of cells in the body to insulin, which means that less insulin is needed to transport glucose into cells. Sulfonylureas indirectly activates the GLUT2 receptor, increases glucose uptake, mitochondrial glycolysis.
- Reduce glucose production: In addition to stimulating insulin secretion, sulfonylureas can also reduce glucose production in the liver, although this effect is less pronounced than with other drugs such as metformin.
Overall, the mechanism of action of sulfonylureas helps to increase insulin secretion and improve insulin sensitivity, leading to lower blood glucose levels in people with type 2 diabetes.
Explanation: Glitazones, also known as thiazolidinediones, are a class of oral hypoglycemic drugs used to treat type 2 diabetes mellitus. They work by improving insulin sensitivity in cells, particularly in adipose tissue and muscle cells. Here is a more detailed explanation of the mechanism of action of glitazones:
- Activate peroxisome proliferator-activated receptor-gamma (PPAR-gamma): Glitazones bind to and activate PPAR-gamma, a nuclear receptor found in adipose tissue, muscle cells, and other cells throughout the body. Activation of PPAR-gamma increases the expression of genes involved in glucose metabolism and insulin sensitivity.
- Increase insulin sensitivity: By activating PPAR-gamma, glitazones increase the sensitivity of cells in the body to insulin. This means that cells are better able to take up glucose from the bloodstream in response to insulin, leading to lower blood glucose levels.
- Decrease glucose production: Glitazones can also decrease glucose production in the liver, although this effect is less pronounced than with other drugs such as metformin.
- Inhibit alpha-glucosidase enzymes: Acarbose inhibits the activity of alpha-glucosidase enzymes in the small intestine. These enzymes are responsible for breaking down carbohydrates into simpler sugars such as glucose.
- Slow carbohydrate absorption: By inhibiting alpha-glucosidase enzymes, acarbose slows down the breakdown and absorption of carbohydrates in the small intestine. This means that glucose is released more slowly into the bloodstream, leading to a smaller rise in blood glucose levels after meals.
- Reduce postprandial hyperglycemia: The slower absorption of glucose from food helps to reduce postprandial hyperglycemia, which is a characteristic feature of type 2 diabetes.
Insulin plays a critical role in carbohydrate metabolism by regulating glucose levels in the blood and promoting glucose uptake by cells. Here are some of the effects of insulin on carbohydrate metabolism:
- Stimulates glucose uptake: Insulin stimulates glucose uptake by cells, particularly muscle and fat cells, by promoting the translocation of glucose transporters (GLUT4) to the cell membrane. This increases the uptake of glucose from the bloodstream into cells, leading to a decrease in blood glucose levels.
- Promotes glycogen synthesis: Insulin promotes the synthesis of glycogen, a storage form of glucose, in liver and muscle cells. Glycogen is formed by linking glucose molecules together into long chains, which can be broken down and released as glucose when the body needs energy.
- Inhibits gluconeogenesis: Insulin inhibits the production of glucose by the liver through a process called gluconeogenesis. This helps to prevent excess glucose production and maintain normal blood glucose levels.
- Increases glycolysis: Insulin increases the activity of glycolysis, a metabolic pathway that breaks down glucose into pyruvate, which can be further metabolized to produce energy.
13-d) Increased protein synthesis
Explanation: Insulin plays a key role in regulating protein synthesis in the body. Here are some of the effects of insulin on protein metabolism:
Stimulates amino acid uptake: Insulin stimulates the uptake of amino acids by muscle cells, which are essential for protein synthesis. Amino acids are the building blocks of proteins and are needed for muscle growth and repair.
Activates protein synthesis: Insulin activates the process of protein synthesis by stimulating the activity of ribosomes, which are cellular structures responsible for assembling proteins. Insulin also activates the protein kinase Akt, which plays a key role in protein synthesis.
Inhibits protein breakdown: Insulin inhibits protein breakdown by suppressing the activity of enzymes that break down proteins, such as proteases. This helps to preserve muscle mass and prevent muscle wasting.
Promotes cell growth: Insulin promotes cell growth by stimulating the activity of growth factors, which are proteins that stimulate cell division and growth. This helps to support muscle growth and repair.
14-a) Increased lipogenesis
Explanation: Insulin plays an important role in lipid metabolism, which involves the synthesis, storage, and breakdown of fats in the body. Here are some of the effects of insulin on lipid metabolism:
- Stimulates lipogenesis: Insulin stimulates the synthesis of fatty acids and triglycerides in the liver and adipose tissue through a process called lipogenesis. This involves the conversion of glucose to fatty acids, which are then packaged into triglycerides and stored in adipose tissue.
- Inhibits lipolysis: Insulin inhibits lipolysis, which is the breakdown of stored triglycerides into fatty acids and glycerol. This helps to prevent the release of excess free fatty acids into the bloodstream, which can interfere with glucose uptake by cells and contribute to insulin resistance.
- Increases fat storage: Insulin promotes the storage of fat in adipose tissue by stimulating the uptake of fatty acids and triglycerides and inhibiting their release into the bloodstream.
- Decreases fat oxidation: Insulin decreases the oxidation of fatty acids for energy, which means that more glucose is used for energy production instead. This helps to conserve stored fat for future energy needs.
- Promotes VLDL synthesis: Insulin promotes the synthesis of very low-density lipoprotein (VLDL), which is a type of lipoprotein that transports triglycerides from the liver to adipose tissue for storage.
Normally, the pH of blood is slightly alkaline, with a range of 7.35-7.45. In ketoacidosis, the pH of the blood can drop below 7.3, indicating a state of metabolic acidosis. The decrease in pH occurs due to the accumulation of ketone bodies in the blood, which can cause an increase in the production of hydrogen ions (H+) and a decrease in bicarbonate ions (HCO3-).
In normal physiological conditions, the polyol pathway is relatively inactive. However, in conditions of hyperglycemia, such as diabetes, the activity of aldose reductase is increased, leading to increased conversion of glucose to sorbitol. This can lead to the accumulation of sorbitol in various tissues, which can cause cellular damage.
HbA1c is an important test for monitoring long-term blood glucose control in individuals with diabetes. It is a more reliable indicator of blood glucose control than a single blood glucose measurement, which can be affected by various factors such as stress, illness, and food intake. HbA1c is also used to diagnose diabetes and to monitor the effectiveness of diabetes treatment over time.
The American Diabetes Association (ADA) recommends that people with diabetes aim for an HbA1c level below 7%.
Lipoprotein lipase breaks down triglycerides (a type of fat) that are carried in the bloodstream by lipoproteins such as chylomicrons and very-low-density lipoproteins (VLDLs). Insulin promotes the activity of lipoprotein lipase by stimulating the expression of the enzyme and increasing its transport to the surface of cells. This results in an increased uptake of triglycerides into cells, where they can be used for energy or stored as fat.
On the other hand, hormone-sensitive lipase breaks down triglycerides that are stored in fat cells into fatty acids and glycerol, which are released into the bloodstream and used by the body for energy. Insulin inhibits the activity of hormone-sensitive lipase by reducing the expression of the enzyme and decreasing its transport to the surface of cells. This helps to prevent the breakdown of stored fat when glucose is available as an energy source.
Glucokinase is an enzyme that is involved in the first step of glucose metabolism in the liver. Glucokinase converts glucose to glucose-6-phosphate, which can then be used in the production of glycogen or energy. Glucokinase has a high affinity for glucose and is only active when glucose levels are high, such as after a meal. Insulin and glucokinase work together to regulate glucose metabolism in the liver. When glucose levels are high, insulin stimulates the production of glucokinase and increases its activity. This helps to promote the conversion of glucose to glucose-6-phosphate, which can be used for energy or stored as glycogen.
Insulin plays an important role in regulating the activity of fatty acid synthase (FAS), an enzyme that is involved in the synthesis of fatty acids. Insulin also stimulates the production of fatty acids by activating the enzyme fatty acid synthase. Fatty acid synthase converts acetyl-CoA and malonyl-CoA to palmitic acid, the primary building block of most fatty acids. Insulin stimulates the production of fatty acids by increasing the expression of fatty acid synthase and activating the enzyme through the addition of phosphate groups. Insulin also increases the availability of acetyl-CoA, the precursor for fatty acid synthesis, by stimulating the breakdown of glucose and other sugars.
In people with type 2 diabetes, there is often a decrease in the sensitivity of cells to insulin, known as insulin resistance. This can lead to a decrease in the production and activity of fatty acid synthase, which can contribute to a decrease in fatty acid synthesis and an increase in fat accumulation in the liver and other tissues.
The recommended lipid levels for people with diabetes are:
Very good brief of glucose metabolism and how insulin hormone is a life saving in our daily life.ReplyDelete
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