Pregledni rad
Pathophysiology of the Metabolic Syndrome
Lea Smirčić-Duvnjak
Sažetak
Although the pathophysiology of the
metabolic syndrome is extremely complex and not completely
understood, insulin resistance and central obesity have
been recognised as the most important pathogenic factors.
Both conditions are independently associated with glucose
intolerance, type 2 diabetes, dyslipidaemia, hypertension,
prothrombotic and proinfl ammatory states and endothelial
dysfunction. Insulin resistance could be defi ned as the
inability of insulin to produce its numerous actions, in
spite of unimpaired secretion from the beta cells. It could
be caused by various genetic and acquired conditions,
including insulin receptor gene, glucose transporters and
signalling proteins mutation, insulin receptor antibodies,
fat diet, inactivity, age and drug infl uence, glucotoxicity,
lipotoxicity.
Except in a few rare cases involving antibodies to the
insulin receptor or mutations in the insulin receptor gene,
the insulin resistance of the metabolic syndrome results
from impairments in cellular events distal to the interaction
between insulin and its surface receptor. The molecular
basis of this syndrome is not completely understood,
although signifi cant progress has been made in recent
years toward an understanding of the intracellular signalling
events that mediate insulin action. Metabolic abnormalities
result from the interaction between the effects of insulin
resistance located primarily in muscle and adipose tissue
and adverse impact of the compensatory hyperinsulinemia
on tissues that remain normally insulin sensitive. The
clinical heterogeneity of the metabolic syndrome can
be explained by its signifi cant role on glucose, fat and
protein metabolism, cellular growth and differentiation and
endothelial function.
Although adiposity has been traditionally defi ned as an
increase in total body mass, cardiovascular risk is associated
with visceral fat accumulation. Visceral fat, in comparison
to subcutaneous tissue, represents a metabolically active
organ, strongly related to insulin sensitivity. Moderating the
secretion of various adipocytokines like leptin, adiponectin,
PAI-1, TNF-alpha, IL-6, resistin, it is associated with the
processes of infl ammation, endothelial dysfunction and
atherogenesis.
Some controversies exist around the key central role of the
metabolic syndrome between insulin resistance and visceral
adiposity. From the practical point of view, it seems there is
no need to dissociate the two conditions. Insulin resistance
is considered to be at the core of the syndrome, while central
obesity is the most prevalent clinical manifestation.
Ključne riječi
insulin; insulin receptor; insulin resistance; hyperinsulinemia; visceral adiposity
Hrčak ID:
19007
URI
Datum izdavanja:
15.11.2004.
Posjeta: 5.779 *