Osteopenia in rats with liver cirrhosis: beneficial effects of IGF-I treatment

Cemborain, Arantxa; Castilla‐Cortázar, Inma; García, María del Carmen Macías; Quirog, Jorge; Muguerza, Begoña; Picardi, Antonio; Santidrian, Santiago; Prieto, Jesús

doi:10.1016/s0168-8278(98)80211-0

Cited by 80 publications

(64 citation statements)

References 32 publications

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“…IGF-1 levels in patients with cirrhosis are also related to the severity of liver disease as measured by the Child-Pugh score. 13 However, a direct causal link between IGF-1 levels and osteoporosis in chronic liver disease in humans has not been established.…”

Section: Pathophysiology Of Osteoporosismentioning

confidence: 99%

Bone disorders in chronic liver disease

2007

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Osteomalacia rarely occurs in adult patients with chronic liver disease despite a low serum vitamin D level being reported in up to two-thirds of patients with cirrhosis. In contrast, osteoporosis, which increases the risk of vertebral fractures, occurs in 12%-55% of patients with cirrhosis. Although the prevalence is probably falling, as shown by a fall from 57%-26% in patients with biliary disease requiring liver transplantation over the last 2 decades, it still accounts for significant patient morbidity. Bone density also falls in the first 3 months after liver transplantation, and pretransplant fractures are predictive of posttransplant fractures. Many of the known risk factors for postmenopausal osteoporosis exist in the cirrhotic population, such as excess alcohol intake, steroid use, poor nutrition, and hypogonadism. There is also an increased risk of osteoporosis in patients without cirrhosis, particularly those with hemochromatosis and biliary disease. The diagnosis is made with bone density measurements. The effective treatment is largely based on evidence from postmenopausal osteoporosis as there have been only a few small clinical trials of patients with chronic liver disease. Bisphosphonates are the mainstay of treatment; they have been shown to be effective in biliary disease and are well tolerated. (HEPATOLOGY 2007;46:1271-1278

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Section: Pathophysiology Of Osteoporosismentioning

confidence: 99%

Bone disorders in chronic liver disease

2007

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“…It has been shown that low doses of IGF1 improve the nutritional status, osteopenia, hypogonadism and liver function tests in rats with hepatic cirrhosis induced by chronic exposure to CCl4 (2)(3)(4)(5)(6)18). Combining the therapeutic potential of recombinant IGF1 in a rat model of liver cirrhosis with the efficiency of rAAV-mediated gene transfer into skeletal muscle could provide an interesting model of gene therapy for liver disease with potential clinical applications.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that low doses of Insulin-like Growth Factor 1 (lGF1), a growth factor synthesised primarily in the liver, improves nutritional status, osteopenia, testicular atrophy and liver function in rats with hepatic cirrhosis induced by chronic exposure to CCI 4 , an organic compound which shows strong hepatic toxicity (2)(3)(4)(5)(6)18). Protein infusion, however, requires substantial amounts of the recombinant protein, which must be administered as a bolus twice a day, These factors limit the potential application of this strategy to cirrhotic patients.…”

mentioning

confidence: 99%

IGF1 gene transfer into skeletal muscle using recombinant adeno-associated virus in a rat model of liver cirrhosis

Zaratiegui

Castilla‐Cortázar

García

et al. 2002

J. Physiol. Biochem.

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Systemic administration of recombinant IGF1 at low levels has been shown to improve hepatic function, nutritional status and testicular atrophy in rats with CCl4-induced cirrhosis. We have developed a recombinant adeno-associated (rAAV) viral vector containing the cDNA for rat IGF1 and confirmed the expression of IGF1 after intramuscular injection of this vector in a rat model of liver cirrhosis. Although weight of injected muscles was significantly increased in rats with mild cirrhosis, this was not the case in rats with advanced, de-compensated cirrhosis. Furthermore, we found no significant amelioration of liver damage in treated rats at any stage of liver cirrhosis. Our results suggest that IGF1 gene transfer into muscle results in a local effect, at least at the vector dose employed here.

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“…Among the endocrine disorders found in CLD, a pivotal role is played by impairment of GH-IGF-1 axis, upon which many metabolic and nutritional abnormalities depend [62][63][64][65][66]. The entire spectrum of GH-IGF-1 axis abnormalities in CLD is referred to as 'acquired GH resistance', and is characterized by low plasma levels of IGF-1, despite normal or elevated serum concentrations of GH.…”

Section: Gh Resistancementioning

confidence: 99%

Diabetes in chronic liver disease: from old concepts to new evidence

Picardi

D’Avola

Gentilucci

et al. 2006

Diabetes Metab. Res. Rev.

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101

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SummaryThe liver is one of the principal organs involved in glucose metabolism together with skeletal muscle and adipose tissue. A link between diabetes and chronic liver disease (CLD) was first observed in the early half of the last century, but to date several questions remain unsolved. Altered glucose tolerance has been well described in alcoholic CLD, non-alcoholic fatty liver disease, chronic hepatitis C and portal hypertension. Moreover, insulin resistance is assuming an ever-growing importance in CLD; chronic hepatitis C has recently been proposed as a metabolic disease and insulin sensitivity as a predictive factor for liver fibrosis.CLD is also complicated by acquired growth hormone (GH) resistance, characterized by low concentrations of insulin-like growth factor-1 (IGF-1) with respect to normal or elevated GH levels. GH resistance in CLD is determined by several factors, including malnutrition, impaired liver function and reduced expression of hepatic GH receptors. We recently described the possible role of tumour necrosis factor-alpha (TNF-α) in blunting the hepatic response to GH in patients with chronic hepatitis C. The role of GH in impaired glucose metabolism is well known, and recent evidence suggests a receptor and/or post-receptor modulation of insulin signalling. Moreover, as in other chronic inflammatory conditions, pro-inflammatory cytokines may directly modulate the signal cascade that follows insulin binding to its receptor in the course of CLD.In this review, the proposed links between impaired glucose tolerance and CLD are analysed, special emphasis being focussed on the most recent findings concerning the interplay of chronic inflammation, GH resistance and insulin resistance.

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Osteopenia in rats with liver cirrhosis: beneficial effects of IGF-I treatment

Cited by 80 publications

References 32 publications

Bone disorders in chronic liver disease

Bone disorders in chronic liver disease

IGF1 gene transfer into skeletal muscle using recombinant adeno-associated virus in a rat model of liver cirrhosis

Diabetes in chronic liver disease: from old concepts to new evidence

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