How does homeostasis control blood glucose levels

Rethinking the role of the brain in glucose homeostasis and diabetes pathogenesis. J Clin Invest 8 —7. How should we think about the role of the brain in glucose homeostasis and diabetes? Diabetes 66 7 — Convergence of pre- and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus. Diabetes 50 12 — Glucokinase is a critical regulator of ventromedial hypothalamic neuronal glucosensing. Diabetes 55 2 — Diabetes 53 3 — Metabolic sensors mediate hypoglycemic detection at the portal vein.

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Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids. J Lipid Res 55 9 — They also slow the rate of absorption of nutrients into the bloodstream by reducing gastric emptying, and they may also help decrease food intake by increasing satiety. People with type 2 diabetes have lower than normal levels of incretins, which may partly explain why many people with diabetes state they constantly feel hungry.

After research showed that BG levels are influenced by intestinal hormones in addition to insulin and glucagon, incretin mimetics became a new class of medications to help balance BG levels in people who have diabetes. Each peptide is broken down by naturally occurring enzymes called DDP-4, dipeptidyl peptidase Exenatide Byetta , an injectable anti-diabetes drug, is categorized as a glucagon-like peptide GLP-1 and directly mimics the glucose-lowering effects of natural incretins upon oral ingestion of carbohydrates.

The administration of exenatide helps to reduce BG levels by mimicking the incretins. Both long- and short-acting forms of GLP-1 agents are currently being used. A new class of medications, called DPP4 inhibitors, block this enzyme from breaking down incretins, thereby prolonging the positive incretin effects of glucose suppression.

An additional class of medications called dipeptidyl peptidase-4 DPP-4 inhibitors—note hyphen , are available in the form of several orally administered products. These agents will be discussed more fully later. People with diabetes have frequent and persistent hyperglycemia, which is the hallmark sign of diabetes.

For people with type 1 diabetes, who make no insulin, glucose remains in the blood plasma without the needed BG-lowering effect of insulin. Another contributor to this chronic hyperglycemia is the liver. When a person with diabetes is fasting, the liver secretes too much glucose, and it continues to secrete glucose even after the blood level reaches a normal range Basu et al.

Another contributor to chronic hyperglycemia in diabetes is skeletal muscle. After a meal, the muscles in a person with diabetes take up too little glucose, leaving blood glucose levels elevated for extended periods Basu et al.

The metabolic malfunctioning of the liver and skeletal muscles in type 2 diabetes results from a combination of insulin resistance, beta cell dysfunction, excess glucagon, and decreased incretins.

These problems develop progressively. Early in the disease the existing insulin resistance can be counteracted by excess insulin secretion from the beta cells of the pancreas, which try to address the hyperglycemia. The hyperglycemia caused by insulin resistance is met by hyperinsulinemia. Eventually, however, the beta cells begin to fail. Hyperglycemia can no longer be matched by excess insulin secretion, and the person develops clinical diabetes Maitra, How would you explain to your patient what lifestyle behaviors create insulin resistance?

In type 2 diabetes, many patients have body cells with a decreased response to insulin known as insulin resistance. This means that, for the same amount of circulating insulin, the skeletal muscles, liver, and adipose tissue take up and metabolize less glucose than normal.

Insulin resistance can develop in a person over many years before the appearance of type 2 diabetes. People inherit a propensity for developing insulin resistance, and other health problems can worsen the condition. For example, when skeletal muscle cells are bathed in excess free fatty acids, the cells preferentially use the fat for metabolism while taking up and using less glucose than normal, even when there is plenty of insulin available.

In this way, high levels of blood lipids decrease the effectiveness of insulin; thus, high cholesterol and body fat, overweight and obesity increase insulin resistance. Physical inactivity has a similar effect. Sedentary overweight and obese people accumulate triglycerides in their muscle cells.

This causes the cells to use fat rather than glucose to produce muscular energy. Physical inactivity and obesity increase insulin resistance Monnier et al. For people with type 1 diabetes, no insulin is produced due to beta cells destruction. Triggers of that autoimmune response have been linked to milk, vaccines, environmental triggers, viruses, and bacteria. For people with type 2 diabetes, a progressive decrease in the concentration of insulin in the blood develops.

Not only do the beta cells release less insulin as type 2 diabetes progresses, they also release it slowly and in a different pattern than that of healthy people Monnier et al.

Without sufficient insulin, the glucose-absorbing tissues—mainly skeletal muscle, liver, and adipose tissue—do not efficiently clear excess glucose from the bloodstream, and the person suffers the damaging effects of toxic chronic hyperglycemia. At first, the beta cells manage to manufacture and release sufficient insulin to compensate for the higher demands caused by insulin resistance.

Eventually, however, the defective beta cells decrease their insulin production and can no longer meet the increased demand. At this point, the person has persistent hyperglycemia. A downward spiral follows. The hyperglycemia and hyperinsulinemia caused by the over-stressed beta cells create their own failure.

In type 2 diabetes, the continual loss of functioning beta cells shows up as a progressive hyperglycemia. How would you explain insulin resistance differently to someone with type 1 diabetes and someone with type 2 diabetes? Together, insulin resistance and decreased insulin secretion lead to hyperglycemia, which causes most of the health problems in diabetes.

The acute health problems—diabetic ketoacidosis and hyperosmolar hyperglycemic state—are metabolic disorders that are directly caused by an overload of glucose. In comparison, the chronic health problems—eye, heart, kidney, nerve, and wound problems—are tissue injury, a slow and progressive cellular damage caused by feeding tissues too much glucose ADA, Hyperglycemic damage to tissues is the result of glucose toxicity.

There are at least three distinct routes by which excess glucose injures tissues:. If you are attending a virtual event or viewing video content, you must meet the minimum participation requirement to proceed. If you think this message was received in error, please contact an administrator. Return to Course Home. Fuels of the Body To appreciate the pathology of diabetes, it is important to understand how the body normally uses food for energy.

Hormones of the Pancreas Regulation of blood glucose is largely done through the endocrine hormones of the pancreas, a beautiful balance of hormones achieved through a negative feedback loop. The glucose becomes syrupy in the bloodstream, intoxicating cells and competing with life-giving oxygen.

If you don't eat for a long time or take a lot of exercise the blood sugar levels could fall dangerously low. It is important that the level of glucose in your blood often called the blood sugar level is controlled so that it does not rise too high or fall too low. This control is brought about by the pancreas, an organ which makes enzymes for the digestive system and hormones to control the blood glucose levels. Eating food raises your blood sugar levels - and carbohydrate foods like these make it rise particularly quickly.

Your pancreas constantly monitors and controls your blood sugar levels using two hormones. The best known of these is insulin.