Clinical and Molecular Hepatology (대한간학회지)

The Korean Association for the Study of the Liver (대한간학회)
권호 표지

Insulin Resistance in Non-Alcoholic Fatty Liver Disease

인슐린저항성과 비알코올성 지방간질환

Park, Jeong-Hyun
박정현

  • Published : 20060000
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Abstract

Insulin resistance is the pathophysiological hallmark of various kinds of clinical diseases, including non- alcoholic fatty liver disease. Insulin resistance is the common characteristic of metabolic syndrome and its related features. Insulin resistance is a systemic disease that affects the nervous system, muscles, pancreas, kidney, heart and immune system, in addition to the liver. A complex interaction between genes and environment factors enhances insulin resistance and the phenotypic expression of NAFLD (non- alcoholic fatty liver disease) in individual patients. Advanced fibrotic liver disease is associated with many features of metabolic syndrome, and the risk of progressive liver disease should not be underestimated for the individuals suffering with metabolic disorders. Abnormalities of insulin signaling can cause the state of insulin resistance, but there is no clear cut scientific evidence that distorted insulin signaling is the primary pathophysiological defect. Increased adipose tissue mass can cause peripheral tissue insulin resistance via the changes of the adipocytokine secretory patterns. We discuss in this article the sequences of the insulin signaling cascades and the possible molecular targets of insulin resistance, the humoral "cross talk" between the distorted secretory patterns of the adipocytokines, and the peripheral tissue insulin resistance along with the pathophysiology of NAFLD.

NAFLD의 병태생리에 있어 인슐린저항성이 긴밀하게 관련되어 있다고 하는 사실을 가장 과학적으로 강력하게 증명하는 것은 최근 이루어진 임상연구 결과들이라고 본다. 간에서 포도당 대사를 억제하는 metformin이 나 특히 말초조직에서 인슐린 저항성을 개선하는 기능을 가진 PPAR-v agonist를 투여해서 임상적인 호전이 나타난 것을 증명한 연구들은, 인슐린저항성이 NAFLD의 발생에서 매우 중요한 역할을 한다는 것을 직접적으로 증명하였다고 볼 수 있다. 인슐린저항성 및 대사 증후군은 전신적인 질환이며， 상태이다. 이것은 mitochondrial injury와， 신경계， 근육， 췌장， 신장， 심장 및 면역계 모두에 광범위한 변화를 초래한다. 인슐린저항성과 NAFLD의 발생과정에는 비만을 초래하는 다양한 환경적인 요인들과 함께 유전적인 요인 역시 강하게 작용하는 것으로 알려져 있다 외견상 동일한 위험인자를 가지고 있어도 어떤 환자는 간 조직에 단순한 지방의 침착만 일어나는 데 반해 다른 환자는 심한 NAFLD를 나타낼 수 있다는 점이 바로 유전적인 요인 역시 중요한 임상적 의미를 가진다는 증거가 될 수 있다. 하지만 지금까지 인슐린저항성에 관여할 것으로 추정되는 유전자 변이가 400여개 이상 발견되었고, 지금도 계속 발견되고 있지만 이들 유전자 단독으로 이러한 질환들이 발생되지는 않는다는 것이 최근의 지배적인 견해다. 소위 gene-environmental interaction에 의해 취약한 유전적 소인을 가진 개인이 환경적인 요인들에 노출되었을 때 이러한 질환들이 발생된다는 시각이다. 이것은 그만큼 이러한 질환들의 병태생리를 연구하는 일 자체가 대단히 어렵다는 것을 의미할 수 있다. NAFLD는 인슐린저항성의 한 부분으로 이해되어야 한다. 개개인에 따라 비록 인슐린저항성의 정도는 유사해도 실제 간질환의 정도는 다를 수 있어, 이것이 개인적인 취약성 (susceptibility )의 차이라고 할 수는 있지만 그 차이는 인슐린저항성이 없는 정상적인 상태에서는 아무런 임상적 의미가 없는 미미한 차이일 수 있다고 본다. 한 개인에서 NAFLD의 존재는 그 개인이 인슐린저항성을 가지고 있다는 것을 시사하는 것으로 받아들여져야 하며, 또한 인슐린저항성을 가진 개인에서는 NAFLD가 존재하거나 향후 나타날 수 있음을 시사하는 것으로 인식되어야 한다고 생각한다.

Keywords

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