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Diabetes in Humans
type 1, 2 and 3


Leo Rogier Verberne


1. Regulation of the blood glucose concentration

A complex regulatory system in the body keeps the blood glucose concentration stable: normal 24-hour variations in humans have a minimum of 4 and a maximum of 8 mmol glucose per litre blood (1).

Pancreas
The pancreas is the main organ in the regulation of the blood glucose level. It is a small gland in the upper belly with a dual function: production of enzymes and hormones. The gland vesicles produce enzymes that are needed for the digestion of food in the bowel. Hormone production takes place in the so-called ‘islets of Langerhans’ that are located between the gland vesicles. In these islets, the α-cells (25%) produce the hormone glucagon, while the β-cells (60%) generate insulin (1). Other cell types (15%) supply hormones that are not considered here. The β-cells monitor the glucose concentration in the blood (2) and maintain this at a level between 4 and 8 mmol/l. If that concentration rises above a normal average, then the β-cells respond by releasing insulin, which lowers the blood glucose concentration. If the concentration drops below the normal average, then the β-cells activate the α-cells to release glucagon, which elevates the blood glucose concentration.

Glucagon
In healthy people, the blood glucose level in the morning (on an empty stomach) is between 4 and 6 mmol per litre blood. Even if they proceed to refrain from eating all day and only drink water, the blood glucose level will not fall to below 4.0. This because the α-cells will then produce glucagon which releases glucose from reserves in the liver, muscles and fat depots. As a result, the blood sugar level is kept at the minimum level (1). So glucagon increases the blood glucose concentration.

Insulin
The blood glucose level in humans does not exceed 8 mmol/l, even if they consume large amounts of sugar and other carbohydrates (1). To that end, the β-cells release an insulin pulse about every six minutes (3). The amount of insulin released, is geared to the rise of the glucose level: the faster the blood value increases, the more insulin the β-cells produce. Insulin opens the ‘glucose gates’ in the organ membranes so that glucose can flow in from the blood. The more hormone secreted by the β-cells, the further the gates open up and the more glucose is absorbed by the organs (4). And thus the organs are fueled with glucose as the blood level drops. An excess of blood sugar is mainly stored in the liver and fat depots.

Physical exercise
Physical exercise increases the sensitivity of the glucose gates for insulin. As a result, the gates will open up further at the same insulin level and thus more glucose will flow into the organs, making the blood level drop even more. But if there is not any insulin at all in the blood (as in untreated juvenile diabetics), then the glucose gates will remain closed even during and after physical exercise. As a result, the blood glucose level in untreated juvenile diabetics will remain as high as it was before exercise.

Incretin-effect
If healthy test subjects drink a solution of glucose after fasting, then their blood sugar level will increase to a maximum value in about one hour. After another hour, the level is back to its starting point. But if the same amount of glucose is administered in a drip, then the blood sugar level will immediately increase. However, it will take longer to restore to the starting value. Apparently the β-cells produce less insulin following a glucose-drip than is the case with consumption of a glucose solution. This difference is referred to as the incretin-effect (3). Incretin is the substance that is released from the intestinal wall if glucose is absorbed from the intestine. It is actually made up of two hormones that stimulate the β-cells in the pancreas to secrete insulin. The more glucose that passes through the intestinal wall, the larger the amount of hormones released and the more the β-cells are stimulated to produce insulin. These intestinal hormones play no role when glucose is administered using a drip. Thus the incretin-effect explains the difference in the course of the blood glucose concentration between drink and drip.

Kidney threshold
When the blood glucose concentration rises above the kidney threshold (11.0 mmol/l), then glucose is excreted with the urine. This condition is referred to as ‘manifest diabetes’. But if the insulin secretion by the β-cells is severely inadequate and the blood glucose level goes into a steep rise, then the excretion of glucose with the urine will not suffice to maintain the blood level at 11.0 mmol/l: the glucose concentration will continue to increase, because the excretion-capacity of the kidneys is inadequate. If insulin is virtually lacking (as in untreated juvenile diabetics), then the blood sugar level, following meals full of carbohydrates and/or after large amounts of sugary drinks, can rise to values over 60 mmol/l (3).

Conclusions
1. The normal blood glucose concentration varies in the course of a 24-hour period from a minimum of 4 to a maximum of 8 mmol/l.
2. The blood glucose concentration is regulated by the β-cells in the pancreas, which produce insulin and regulate the release of glucagon by the α-cells.
3. Physical exercise renders the glucose gates in organ membranes more sensitive to insulin thus promoting the absorption of blood glucose in the organs, as a result of which the blood level drops.
4. The incretin-effect is the stimulation of insulin secretion in the pancreas by intestinal hormones.
5. In the event of a severe lack of insulin, the excretion capacity of the kidneys for glucose is not sufficient to maintain the blood glucose level at the kidney threshold.

References
1. Guyton AC and Hall JE. Insulin, glucagon and diabetes mellitus. In: Textbook of Medical Physiology 12th ed.(2011); ISBN 978-1-4160-4574-8; p 939-954
2. Koning E de (2012). Voordracht nationale diabetesdag.
3. Tack CJ en Stehouwer CDA. Diabetes mellitus. In: Interne geneeskunde. eds. Stehouwer, Koopmans en van der Meer. 14e druk (2010); ISBN 978-90-313-7360-4; p 835-865
4. Wikipedia.en (2016) Insulin

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© Leo Rogier Verberne
ISBN/EAN:978-90-825495-4-6
www.diabetesbook.org


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