Physiopathology of endocrine pancreas. Insulin deficiency

Insulin deficiency

Insulin deficiency is the main cause of insulin-dependent diabetes pathogeny or type I diabetes.
Type I diabetes Mellitus is related to insulin deficiency consecutive to reduction of beta-pancreatic cells population. One of the major causes of diabetes Mellitus is inflammation with autoimmune alteration of Lagerhans islets (insulite). It has a specific and exclusive localisation in islets formed of beta cells, while in islets formed of glucagon producing cells inflammation is missing.

Insulin deficiency produces multiple metabolic disturbances with specific severe lesions of body structure.
Glycogen and lipid synthesis disturbances constitutes the basic and essential metabolic manifestation of insulin deficiency.
These are related with insulin/glucagon index.

The consequence of this thing is the impossibility of liver and muscles to synthesise glycogen and of adipocites to synthesise lipids from glucose.
Cardinal clinical signs of type I diabetes: reduced glucose tolerance, hyperglycaemia, protein catabolism intensification, hyperlipidemia, angiopathy and nephrotic syndrome.


The pathogenesis of hyperglycaemia is the fact that in the absence of insulin,  insulin-dependent glucose receptors in adipocytes and myocytes type IV reside in the cytoplasm,  are not exposed on the cell membrane, due to which the glucose can not be assimilated by the cells for synthesis of glycogen and fat.

The pathogenesis of hyperlipidemia (prevalent on account of the very low density lipoprotein and non-esterified fatty acids) can be explained by the fact that the lipase in the absence of adipocyte insulin remain phosphorylated, inactive, dietary fat are not incorporated into adipocytes, and unwanted fatty acids are converted in the liver to very low density lipoprotein.Increase blood concentration of non-esterified fatty acids (hyperlipidemia transport) is the consequence of intense mobilization of lipids from adipose tissue.

Hiperketonemia and ketonuria is due to high concentration of fatty acids in the blood with increased beta-oxidation and acetyl CoA abundant production, that in lack of insulin is not used for lipid resynthesis   but ketone bodies - acetone, hydroxybutyric acid and acetylacetic acid synthesis.

Renal syndrome in hypoinsulinism is constituted of  glucosuria due to hyperglycaemia and high glucose concentration in glomerular filtration, which exceeds the functional capacity of the  canalicular epithelium glucokinase (threshold is about 180 mg / dL).

Glucosuria leads polyuria (osmotic diuresis) and polydipsia. Development of diabetic nephropathy with microangiopathy leads to progressive decrease in glomerular filtration rate, with the growth of the permeability of renal filter and albuminuria.
Ketonuria is consecutive to hyperketonemia.

In the pathogenesis of diabetic angiopathy glycosylation of proteins - its IDDM process, which consists in the non-fermentative combination of glucose with amino acids amino-groups to form complexes of glucose and protein (ketone-amino-proteins​​) in the vessel wall .
Glycosylation changes the conformation of the protein molecule, the electric charge, alter the function of proteins, blocking the active center. Diabetic angiopathy is affecting both small vessels and large ones.

Diabetes can lead to coma - ketoacidotic in absolute insufficiency of insulin, hyperosmolar in moderate insulin deficiency and lactoacidotic in hypoxia, sepsis, cardiogenic shock. (An overdose of insulin can result in hypoglycemic coma).
Pathogenetic correction of homeostasis in ketoacidotic coma seeks liquidation of insulin deficiency, and  rehydration and resalinization of the body, restoring acid-base balance and glycogen reserves.