BIO6: Regulation of Glucose

Regulation of Glucose

This is the process by which the levels of blood sugar, primarily glucose, are maintained by the body within a narrow range. This tight regulation is referred to as glucose homeostasis. 

Insulin, which lowers blood sugar, and glucagon, which raises it, are the most well-known of the hormones involved, but more recent discoveries of other glucoregulatory hormones have expanded the understanding of this process.

The human body wants blood glucose (blood sugar) maintained in a very narrow range. Insulin and glucagon are the hormones which make this happen. Both insulin and glucagon are secreted from the pancreas, and thus are referred to as pancreatic endocrine hormones.

The picture on the left shows the intimate relationship both insulin and glucagon have to each other. Note that the pancreas serves as the central player in this scheme.  It is the production of insulin and glucagon by the pancreas which ultimately determines if a patient has diabetes, hypoglycemia, or some other sugar problem.

Insulin basics: How Insulin helps control blood Glucose levels

Insulin and glucagon are hormones secreted by islet cells within the pancreas. They are both secreted in response to blood sugar levels, but in opposite fashion!

Insulin is normally secreted by the beta cells (a type of islet cell) of the pancreas. The stimulus for insulin secretion is a HIGH blood glucose…it’s as simple as that!  Although there is always a low level of insulin secreted by the pancreas, the amount secreted into the blood increases as the blood glucose rises. Similarly, as blood glucose falls, the amount of insulin secreted by the pancreatic islets goes down. 

As can be seen in the picture, insulin has an effect on a number of cells, including muscle, red blood cells, and fat cells.  In response to insulin, these cells absorb glucose out of the blood, having the net effect of lowering the high blood glucose levels into the normal range.

THIS VIDEO IS ABOUT REGULATION OF GLUCOSE

Glucagon is secreted by the alpha cells of the pancreatic islets in much the same manner as insulin…except in the opposite direction. If blood glucose is high, then no glucagon is secreted. 

When blood glucose goes LOW, however, (such as between meals, and during exercise) more and more glucagon is secreted. Like insulin, glucagon has an effect on many cells of the body, but most notably the liver.

The role of Glucagon in blood Glucose control

The effect of glucagon is to make the liver release the glucose it has stored in its cells into the bloodstream, with the net effect of increasing blood glucose. Glucagon also induces the liver (and some other cells such as muscle) to make glucose out of building blocks obtained from other nutrients found in the body (eg, protein).

Our bodies desire blood glucose to be maintained between 70 mg/dl and 110 mg/dl (mg/dl means milligrams of glucose in 100 milliliters of blood). Below 70 is termed “hypoglycemia.” Above 110 can be normal if you have eaten within 2 to 3 hours. 

That is why your doctor wants to measure your blood glucose while you are fasting…it should be between 70 and 110.  Even after you have eaten, however, your glucose should be below 180. Above 180 is termed “hyperglycemia” (which translates to mean “too much glucose in the blood”). If your 2 two blood sugar measurements above 200 after drinking a sugar-water drink (glucose tolerance test), then you are diagnosed with diabetes.  

Anatomy of the pancreas

Insulin lowers blood glucose by increasing the rate of glucose uptake and utilization

Glucagon raises blood glucose by increasing the rates of glycogen breakdown and glucose manufacture by the liver

Glucose regulation and metabolism terms:

– Gluconeogenesis – Synthesis of glucose from noncarbohydrate precursors, Lactic acid, glycerol, amino acids, liver cells synthesis glucose when carbohydrates are depleted
– Glycogenesis – Formation of glycogen, glucose stored in liver and skeletal muscle as glycogen, important energy reserve
– Glycogenolysis – breakdown of glycogen (polysaccharide) into glucose molecules (monosaccharide)
– Glycolysis – the breakdown of glucose into pyruvate by cells for the production of ATP

Blood Glucose Regulation – Glucose, glucagon, and insulin levels over a 24-hour period.

Insulin – Glucagon Summary

Fed-state metabolism under the influence of insulin promotes glucose metabolism by cells

Stimuli for Insulin Secretion

– Increased glucose concentrations
– Increased amino acids concentrations
– Feedforward effects of GI hormones

–Parasympathetic activity
–Sympathetic activity

Multiple Stimuli for Insulin Release

Endocrine Response to Hypoglycemia

Insulin Action

– Increases glucose transport into most, but not all, insulin-sensitive cells
– Enhances cellular utilization and storage of glucose
– Enhances utilization of amino acids
– Promotes fat synthesis

In the absence of insulin, glucose cannot enter the cell

Insulin enables glucose uptake by adipose tissue and resting skeletal muscle

Insulin binds to receptor, initiates the synthesis of glucose transporters (GLUT 4) the GLUT 4 transpor proteins are integrated into the cell membrane allowing glucose to be transported into the cell.

Insulin acts indirectly to alter glucose uptake in hepatocytes: in fed state liver cells take up glucose

A hepatocyte in the fasted state makes glucose and transports it out into the blood

Regulation of Blood Glucose Concentrations.

Chemical Digestion: Carbohydrates

– Salivary and pancreatic enzymes catabolize into disaccharides and trisaccharides
– Brush border cells of the small intestine release enzymes to further catabolize into monosaccharides
– Absorption of monosaccharides occurs across the intestinal epithelia
– Enzymes used: salivary amylase, pancreatic amylase, and brush border enzymes

Carbohydrate Absorption in the Small Intestine:

Absorption: via cotransport with Na+, and facilitated diffusion
Enter the capillary bed in the villi
Transported to the liver via the hepatic portal vein

Normal and Abnormal Results of Glucose Tolerance Tests

Renal Reabsorption of Glucose

– Na+ linked secondary active transport
– Key site – proximal convoluted tubule (PCT)

Reabsorption: Transport Maximum

Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas leading to a deficiency of insulin

Type 2 diabetes mellitus is characterized differently and is due to insulin resistance or reduced insulin sensitivity, combined with relatively reduced insulin secretion which in some cases becomes absolute. The defective responsiveness of body tissues to insulin almost certainly involves the insulin receptor in cell membranes

– Accounts for 90% of all diabetics
– Complications include atherosclerosis, neurological changes, renal failure, and blindness
– Therapy

— Diet and physical exercise
— Drugs

Regulation of Glucose Metabolism During Exercise
– Glucagon secretion increases during exercise to promote liver glycogen breakdown (glycogenolysis)
– Epinephrine and Norepinephrine further increase glycogenolysis
– Cortisol levels also increase during exercise for protein catabolism for later gluconeogenesis.
– Thyroxine promotes glucose catabolism

As intensity of exercise increases, so does the rate of catecholamine release for glycogenolysis
During endurance events the rate of glucose release very closely matches the muscles need
When glucose levels become depleted, glucagon and cortisol levels rise significantly to enhance gluconeogenesis.

Glucose must not only be delivered to the cells, it must also be taken up by them. That job relies on insulin.
Exercise may enhance insulin’s binding to receptors on the muscle fiber.
Up-regulation (receptors) occurs with insulin after 4 weeks of exercise to increase its sensitivity (diabetic importance). 

The effects of exercise on glucose tolerance and insulin secretion 

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