Insulin-like growth factor-binding protein-1 response to insulin during suppression of endogenous insulin secretion

Lee, Phillip; Jensen, Michael D.; Divertie, Gavin D.; Heiling, Valarie J.; Katz, H.; Conover, Cheryl A.

doi:10.1016/0026-0495(93)90095-6

Cited by 36 publications

(11 citation statements)

References 31 publications

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“…In addition, SAD was the sole anthropometric variable that explained the variations in fasting glucose and IGFBP-1 concentrations. The latter accords well with our results, as low IGFBP-1 reflects peripheral insulin resistance (38) and perhaps also hepatic insulin resistance (39). However, of more clinical relevance, low IGFBP-1 is a risk marker of cardiovascular disease (27,28).…”

Section: Statisticssupporting

confidence: 91%

Sagittal Abdominal Diameter Is a Strong Anthropometric Marker of Insulin Resistance and Hyperproinsulinemia in Obese Men

et al. 2004

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OBJECTIVE -It is clinically important to find noninvasive markers of insulin resistance and hyperproinsulinemia because they both predict cardiovascular and diabetes risk. Sagittal abdominal diameter (SAD) or "supine abdominal height" is a simple anthropometric measure previously shown to predict mortality in men, but its association with insulin resistance and hyperproinsulinemia is unknown. RESEARCH DESIGN AND METHODS-In a common high-risk group of 59 moderately obese men (aged 35-65 years, BMI 32.6 Ϯ 2.3 kg/m 2 ), we determined anthropometry (SAD, BMI, waist girth, and waist-to-hip ratio [WHR]); insulin sensitivity (euglycemichyperinsulinemic clamp); and plasma concentrations of intact proinsulin, specific insulin, Cpeptide, glucose, and serum IGF binding protein-1 (IGFBP-1). To compare SAD with other anthropometric measures, univariate and multiple regression analyses were used to determine correlations between anthropometric and metabolic variables.RESULTS -SAD showed stronger correlations to all measured metabolic variables, including insulin sensitivity, than BMI, waist girth, and WHR. SAD explained the largest degree of variation in insulin sensitivity (R 2 ϭ 0.38, P Ͻ 0.0001) compared with other anthropometric measures. In multiple regression analyses, including all anthropometric measures, SAD was the only independent anthropometric predictor of insulin resistance (P Ͻ 0.001) and hyperproinsulinemia (P Ͻ 0.001).CONCLUSIONS -In obese men, SAD seems to be a better correlate of insulin resistance and hyperproinsulinemia (i.e., cardiovascular risk) than other anthropometric measures. In overweight and obese individuals, SAD could represent a simple, cheap, and noninvasive tool that could identify the most insulin resistant in both the clinic and clinical trials evaluating insulin sensitizers. These results need confirmation in larger studies that also include women and lean subjects. Diabetes Care 27:2041-2046, 2004M ore than half of adult Americans are overweight or obese (1). Many, but far from all of those subjects, will suffer from obesity-related diseases. Insulin resistance may be the key factor in obesity that contributes to increased health risk, as the more insulin resistant an individual, the more likely they are to develop diabetes and cardiovascular disease (2-4). Therefore, identification of insulin resistance also is important in moderately obese subjects.Recently, elevated intact proinsulin, reflecting both insulin resistance and ␤-cell dysfunction (5), has emerged as an independent predictor of type 2 diabetes (5-7) and cardiovascular mortality (8,9). However, a simple clinical surrogate marker for hyperproinsulinemia is still to be found.McLaughlin and Reaven (10) recently highlighted the need for a useful tool to identify insulin resistance, as direct measures of insulin resistance are unfeasible for clinical use. While fasting insulin has shown to be a useful estimate of insulin resistance, it is invasive and the lack of standardized assays limits its use (11). Alternatively, triglycerid...

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Section: Statisticssupporting

confidence: 91%

Sagittal Abdominal Diameter Is a Strong Anthropometric Marker of Insulin Resistance and Hyperproinsulinemia in Obese Men

et al. 2004

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“…Estos factores de crecimiento son hormonas anabólicas, marcadores del estatus nutricional y de la función hepática, cuya biodisponibilidad está reducida en la cirrosis del hígado (52)(53)(54). Bajos niveles de IGF1 y altos niveles de IGFBP-1 (proteína de unión al IGF1) han sido descritos previamente en asociación con la cirrosis y la resistencia a la insulina (55,56). La insulina es la principal reguladora de la expresión del IGFBP-1 hepático, mediante un descenso en el plasma del IGFBP-1 en respuesta al estado nutricional.…”

Section: Discussionunclassified

Expresión génica en pacientes obesos con enfermedad hepática por depósito de grasa

Cayón¹,

Crespo

Guerra

et al. 2008

Rev. esp. enferm. dig.

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. Expresión génica en pacientes obesos con enfermedad hepática por depósito de grasa. Rev Esp Enferm Dig 2008; 100: 212-218. RESUMENLa fisiopatología de la enfermedad hepática por depósito de grasa sólo se conoce de forma parcial. En este trabajo hemos analizado la expresión génica intrahepática de citoquinas, quimioquinas, receptores celulares, factores de crecimiento, transductores de señales intracelulares y proteínas de comunicación extracelular en el tejido hepático de sujetos obesos con y sin esteatohepatitis no alcohólica, en un intento de determinar un perfil de expresión génica asociado a las formas severas de la esteatohepatitis no alcohólica (EHNA).Se analizó un grupo de 38 pacientes obesos con un IMC > 35, que fueron sometidos a cirugía bariátrica. La expresión génica intrahepática se determinó en el tejido hepático dividiendo a los pacientes en tres grupos: a) pacientes obesos sin datos histológicos sugestivos de EHNA (n = 12); b) pacientes con EHNA sin fibrosis (n = 13); y c) pacientes con EHNA y fibrosis (n = 13). Se consideró que existía una sobreexpresión génica cuando la diferencia en la expresión era, al menos, de dos veces con respecto al grupo control. Los resultados se confirmaron mediante PCR en tiempo real. Se detectó una expresión diferencial de 14 genes (10 sobreexpresados y 4 infraexpresados). Los genes sobreexpresados incluyeron prohibitina, TNF, TNF RI (p55), MCSF, R2-TRAIL, TGF-b1, CTGF, FGF, VEGF, BIGH3 y ObRb. La expresión de los genes insulin growth factor-1, insulin growth factor-2, interleuquina-2 y tyrosine-receptor fue menor que en el grupo control.En conclusión: 1. Los pacientes obesos con EHNA sin fibrosis muestran una sobreexpresión de genes proinflamatorios y proapoptóticos. En los pacientes con EHNA y fibrosis, se observa, además, una sobreexpresión de genes profibrogénicos, incluyendo el gen del receptor de la leptina.2. La expresión de prohibitiva en los pacientes con EHNA, tanto con fibrosis como sin fibrosis, fue superior que en los controles, lo que sugiere una disfunción mitocondrial en los pacientes con EHNA.Palabras clave: Esteatohepatitis no alcohólica. Enfermedad hepática por depósito de grasa. Obesidad mórbida. ABSTRACTAlthough the molecular basis for the pathophysiology of nonalcoholic steatohepatitis (NASH) is poorly understood, we evaluate the hepatic gene expression of cytokines, chemokines, cell receptors, growth factors, intracellular transducers and extracellular communication proteins in liver tissue of obese patients (with and without NASH), and we determine the specific intrahepatic gene expression profiles associated with histological severe NASH.Thirty-eight obese patients with BMI > 35 were analyzed, who underwent bariatric surgery. Biopsy specimen samples were snapfrozen in liquid nitrogen. Hepatic gene expression was determined in liver biopsy specimens from 3 groups: a) obese patients without NASH (n = 12); b) patients with NASH without fibrosis (n = 13); and c) patients with NASH and fibrosis (n = 13). Genes were considered to be expressed di...

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“…Insulin is the principal regulator of hepatic IGFBP-1 production, mediating a rapid decrease in plasma IGFBP-1 in response to nutritional intake. 48,49 The expected effect of increased IGFBP-1 expression would be of decreased intracellular free IGF-1 availability and subsequent insulin resistance. The finding of increased expression of IG-FBP-1, in the setting of hyperinsulinemia, is thus particularly interesting because overexpression of IGFBP-1 might contribute to insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Hepatic Gene Expression in Histologically Progressive Nonalcoholic Steatohepatitis

et al. 2003

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Although the molecular basis for the pathophysiology of nonalcoholic steatohepatitis (NASH) is poorly understood, insulin resistance and mitochondrial dysfunction are physiologic hallmarks of this condition. We sought evidence of a transcriptional or pretranscriptional basis for insulin resistance and mitochondrial dysfunction through measurement of hepatic gene expression (messenger RNA [mRNA]) using high-density synthetic oligonucleotide microarray analysis (Hu6800 GeneChip, Affymetrix, CA). Global hepatic gene expression was determined in snap-frozen liver biopsy specimens from 4 groups: (1) patients with cirrhotic-stage NASH (n ‫؍‬ 6), (2) patients with cirrhosis caused by hepatitis C virus (HCV) (n ‫؍‬ 6), (3) patients with cirrhosis secondary to primary biliary cirrhosis (PBC) (n ‫؍‬ 6), and (4) healthy controls (n ‫؍‬ 6). Genes were considered to be expressed differentially in NASH only if there was a greater than 2-fold difference in abundance of mRNA when compared with each of the control groups. Sixteen genes were uniquely differentially expressed (4 overexpressed and 12 underexpressed) in patients with cirrhotic-stage NASH. Genes that were significantly underexpressed included genes important for maintaining mitochondrial function (copper/zinc superoxide dismutase, aldehyde oxidase, and catalase). Glucose 6-phospatase, alcohol dehydrogenase, elongation factor-TU, methylglutaryl coenzyme A (CoA), acyl CoA synthetase, oxoacyl CoA thiolase, and ubiquitin also were underexpressed in NASH. Genes that were overexpressed in NASH included complement component C3 and hepatocyte-derived fibrinogen-related protein, potentially contributing to impaired insulin sensitivity. In conclusion, these studies provide evidence for a transcriptional or pretranscriptional basis for impaired mitochondrial function (attenuated capacity for the dismutation of reactive oxygen species) and diminished insulin sensitivity (increased acute phase reactants) in patients with histologically progressive NASH. Further studies are required to determine the mechanism and the physiologic significance of these findings. (HEPATOLOGY 2003;38:244-251.)

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Insulin-like growth factor-binding protein-1 response to insulin during suppression of endogenous insulin secretion

Cited by 36 publications

References 31 publications

Sagittal Abdominal Diameter Is a Strong Anthropometric Marker of Insulin Resistance and Hyperproinsulinemia in Obese Men

Sagittal Abdominal Diameter Is a Strong Anthropometric Marker of Insulin Resistance and Hyperproinsulinemia in Obese Men

Expresión génica en pacientes obesos con enfermedad hepática por depósito de grasa

Hepatic Gene Expression in Histologically Progressive Nonalcoholic Steatohepatitis

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