In the natural history of DMT2, insulin resistance appears first, that is, the
insulin signal is not received in the periphery, so that the β cell must undergo
further insulin secretory work to compensate for reduced insulin efficacy.
To make a comparison, it is as if a person were deaf and an interlocutor had to
raise the volume of the voice to be heard by his friend. Likewise, the beta cell
raises the volume of insulin, but soon exhausts its capacity for secretion and
goes into functional exhaustion.
But when the cat is not there or does not show up, then the mice dance is said
to be danzing!
In fact, if the action of insulin is missing, another hormone takes over,
hormone that normally must be kept apart, just the glucagon, which we know
intervenes to raise the level of blood sugar in the fast. The glucagon is
incresed even when the glucose level is high, such as the mice without cat!
Thus glucagon plays a key role in determining diabetes because the presence of
this hormone, produced by pancreatic α cells, in the periphery determines an
increase in hepatic neoglucogenesis, ie the process that leads to the production
of glucose (cf. carbohydrates).
Finally, in the paronama of diabetes, recently the neglected GLP1,
an hormone produced by the digestive tract and implicated in the trophism of
the beta pancreatic cell and in the inhibition of glucoagone secretion
(cf.
new concept of incretinic therapy) is found. Next to it is an island of Langherans of the human
pancreas, with the pancreatic α, β and δ cells, respectively colored with
immunohistochemistry in green, red and blue.
Pancreatic beta cells of the experimentation with mouse,
up exhausted without treatment with GLP-1.
Beta cells after treatment with GLP-1,
is known hyperplasia of the islets
Diagram of the beta cell and the phenomenon
of exocytosis insulin
The pancreatic isles, called Langherans by the name of the scholar who
identified them in the late nineteenth century, are in the human pancreas at
least a million and represent 1-2% of the mass of the entire organ.
Histologically they appear as ovoid structures, with sizes from a few microns up
to 200-300 μ.
The α cells and pancreatic β cells in humans, unlike other species of mammals, are interlocked with each other on the island of Langherans, associated with the δ cells that produce somatostatin. The islands are endowed with a very rich vascularization, due to their function in view of the metabolism of carbohydrates. In fact, beta cells produce insulin and insulin, as we know, is the key that regulates the metabolism of glucose, that is the hormone that allows the cell to capture inside it the main fuel available to humans, that is glucose, indeed (cf. diabetes). Normal cellular β function depends on the integrity of the mechanisms that regulate insulin synthesis and release, as well as on the total mass of the insulins. In fact, at the time of diagnosis of diabetes (cf. diabetes prevention_diabetes) at least 50% of the cell mass is lost.
Once glucose is in circulation, after the assimilation of food, this molecule is at the base of the mechanisms that lead to the release of insulin. In fact it is believed that glucose enters the beta cell by specific gluco-transporters, in particular GLUT2 and GLUT1; therefore the glucose is phosphorylated by the enzyme glucokinase and then the colitics is started from the chain. The resulting pyruvate enters the mitochondria through the cycle of tricarboxylic acids and the subsequent mitochondrial events in the respiratory chain lead to the production of ATP. The increase in the ATP/ADP ratio induces the closure at the cell membrane level of the dependent ATP potassium channel, which results in the opening of the voltage-dependent calcium channels, with the entry of calcium ions into the cell. The latter mechanism determines the release of insulin through degranulation.
This release recognizes a first rapid phase followed by a prolonged phase; moreover the secretion is pulsatile. As long as the mass of the insulae is conserved or even increased as in the young, everything falls within the physiology of metabolisms. When, however, it goes on over the years, then apoptotic phenomena prevail over cellular regeneration. In the diabetes horizon, a key role is played, again, by the pancreatic alpha cell, which has an antithetical function to the beta and produces glucagon. Glucagon promotes the release of glucose from the liver in the fasting period, that is to say 3-4 hours from the meal, avoiding dangerous hypoglycemic crises. The problem, however, is that in diabetes, when the blood sugar is high even fasting, glucagon is always active and the neoglucogenesis occurs even against high blood glucose levels in the bloodstream. At the level of the target cells the glucagon binds to specific membrane receptors and this event activates the enzyme adenylate cyclase which in turn catalyses the reaction of ATP into cyclic AMP and which in turn activates protein kinases called cyclic AMPs dependent and therefore the phosphorylation of intracellular enzymes responsible for the effect of glucagon. In the diabetic the activity of the alpha cell is exaggerated and so the alpha cell does not recognize the inhibitory stimulus exerted by the high glycaemia. Some authors would also talk about increasing the volume of alpha cells in the diabetic.
This being the case in the diabetic
patient, for the purposes of treatment it should be noted that:
•Beta cells are reduced in number and the beta-cell function goes into
exhaustion
The alpha cells are released from the control exercised by hyperglycaemia and
have a larger volume and an exacerbated function
There is the role of other hormones in glucose metabolism, including GLP-1.
Next to it is represented a laboratory model, that of the Goto_kakizaki rats
where, through the stimulation with GLP-1, a restoration of the mass and
function of beta-pancreatic cells was obtained.