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VOL. 73 (3), 763-784, 2007 FROM PATHOGENESIS TO THERAPEUTIC OF TYPE 2...

el tratamiento del decrecimiento de la masa funcionante de la célula beta lo cual
es encontrada en T2D.

Palabras clave: Diabetes tipo 2.—Rata GK.—Secreción de insulina.—Agonistas
GLP-1R.—Regeneración de células beta.

Diabetes mellitus is a heterogeneous group of disorders
characterized by high blood glucose levels. The pancreatic beta-cell
and its secretory product insulin are central in the pathophysiology
of diabetes (1). Type 1 or insulin-dependent diabetes mellitus results
from an absolute deficiency of insulin due to autoimmune beta-cell
destruction. In type 2, non-insulin-dependent diabetes mellitus (T2D),
liver, muscle and fat cells are resistant to insulin actions and the
compensatory attempt by the beta-cell to release more insulin is
not sufficient to maintain blood glucose levels within a normal
physiological range, finally leading to the functional exhaustion of
the surviving beta-cells (1). T2D is made up of multiple forms each
of which is characterized to variable degrees by insulin resistance
and beta-cell dysfunction, and which together lead to hyperglycemia.
At each end of this spectrum are single-gene disorders that affect the
ability of the beta-cell to secrete insulin or the ability of liver, muscle
and fat cells to respond to insulin’s actions.

BETA-CELL DYSFUNCTION AS A CAUSE FOR HUMAN
TYPE 2 DIABETES

In patients with recognized type 2 diabetes, abnormalities of
secretion are present together with insulin resistance and cause
glucose intolerance. So far, information related to the functional
characteristics of islets from T2D patients is limited. Several groups
(2, 3) have recently reported multiple abnormalities of insulin
secretion in islets isolated from T2D donors such as: reduced insulin
content, poor secretion in response to glucose (whereas leucine,
glutamine or arginine challenge remained effective) associated with
a marked alteration of mitochondrial function (diminished glucose
oxidation, lower ATP/ADP ratio, impaired hyperpolarization of
mitochondrial membrane, increased expression of UCP-2) and signs
of increased oxidative stress. Structural changes in the islets of T2D

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