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Biomedical subjects

Francine H Einstein

Publications and source records attributed to Francine H Einstein.

5 recordsLinked to original sources
PubMed2006

Resistance to leptin action is the major determinant of hepatic triglyceride accumulation in vivo.

Impairment of both insulin and leptin action has been implicated in the pathogenesis of nonalcoholic fatty liver disease. By assessing hepatic triglyceride (TG) stores in response to modulation of leptin action (by leptin infusion), we attempted to determine whether leptin has the major role in hepatic TG accumulation. TG were markedly decreased (by 63%, P<0.05) in young animals treated with leptin. However, this was also associated with improvement in hepatic insulin action (2-fold decrease in HGP during clamp, P<0.05). These effects on hepatic TG stores and insulin action were abolished in old rats who demonstrate leptin resistance. Since these experiments could not discern the role of leptin from the role of hepatic insulin action on hepatic TG stores, we further examined the effect of improvement of hepatic insulin action by visceral fat removal (VF-). Enhancement of hepatic insulin action in old VF-rats was associated with reduced hepatic TG stores (by 64% P<0.01). Because this manipulation may have induced an improvement in leptin action as well, we studied VF removal in a genetically leptin-resistant model (Zucker Diabetic Fatty rats, ZDF). Only in this mode was exclusive improvement of hepatic insulin action by VF removal not associated with reduced hepatic TG stores, suggesting that improved hepatic insulin action is not necessary for modulation of hepatic TG stores. By dissociating action of leptin from that of insulin, we suggest that the failure of leptin action is the major physiological mechanism for hepatic steatosis.

Animals↗
PubMed2006

Central and opposing effects of IGF-I and IGF-binding protein-3 on systemic insulin action.

IGF-I is recognized as an insulin sensitizer at the liver and muscle, while recent evidence suggests that IGF-binding protein (IGFBP)-3 acts as an insulin antagonist. As there is a paucity of IGF-I receptors in the liver and as the IGF-IGFBP system in the central nervous system is emerging as physiologically relevant, we examined whether the effects of IGF-I and IGFBP-3 on insulin action are mediated through central mechanisms. Intracerebroventricular (ICV) infusion of IGF-I during the insulin clamp (3 mU x kg(-1) x min(-1)) resulted in significant improvement in hepatic insulin action (50%, P < 0.05). In contrast, ICV infusion of IGFBP-3 significantly impaired insulin action at the liver (45% increase in hepatic glucose production, P < 0.01). While IGF-I marginally increased peripheral glucose uptake, IGFBP-3 significantly decreased peripheral glucose uptake (approximately 30%, P < 0.01). As the nuclear localization signal mutant IGFBP-3, which has a normal affinity to IGFs but binds other IGFBP-3 partners poorly and fails to normally internalize, has reduced central activity on metabolism, we conclude that the effects of IGFBP-3 on the hypothalamus involve activity mediated by interfacing with other molecules in addition to IGFs. Marked, opposing, and independent physiological effects of IGF-I and IGFBP-3 through central mechanisms may have implications on potential strategies in specific modulation of peripheral insulin action.

Animals↗
PubMed2005

Differential responses of visceral and subcutaneous fat depots to nutrients.

Increased visceral adiposity is a pivotal component of the metabolic syndrome. Differential gene expression patterns of fat-derived peptides (FDPs) in visceral fat and subcutaneous fat have been characterized in the fasting state. Here we examined whether delivery of nutrients differentially affects the expression of FDPs in visceral fat versus subcutaneous fat (in the fed state). We increased the rate of glucose flux into adipose tissue of normal rats (n = 16) by hyperglycemia or hyperinsulinemia using the clamp technique. Glucose uptake was associated with increased expression of FDPs, including resistin ( approximately 5-fold), adiponectin ( approximately 2-fold), leptin ( approximately 15-fold), plasminogen activating inhibitor-1 ( approximately 10-fold), and angiotensinogen ( approximately 4-fold) in visceral fat, but markedly less in subcutaneous fat. Cytokine expression derived mainly from vascular/stromal/macrophage components of adipose tissue was less dramatically increased. Infusion of glucosamine amplified the results obtained by increasing glucose uptake into adipose tissue, suggesting that flux through the hexosamine biosynthetic pathway may serve as a mechanism for "nutrient sensing." Nutrient-dependent expression of FDPs in visceral fat was also associated with increased plasma levels of several FDPs. Because a biologic sensing pathway can dynamically couple daily food intake to abnormal plasma levels of important FDPs, we challenge the practice of obtaining plasma levels after fasting to assess risk factors for metabolic syndrome.

Adipose Tissue↗
PubMed2004

The impact of protease inhibitors on maternal serum screening analyte levels in pregnant women who are HIV positive.

OBJECTIVE: The purpose of this study was to compare alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol levels in women who take protease inhibitors and those women who do not. STUDY DESIGN: This retrospective review from August 2000 to May 2003 was performed for maternal serum screen results, medication use, pregnancy, and perinatal outcomes. RESULTS: Thirty-nine women met study criteria. Sixteen women were treated with protease inhibitors, and 23 women were not treated with protease inhibitors. There was no difference in initial viral load or initial CD4 count between the groups. No difference was found for human chorionic gonadotropin and estriol levels; significantly lower alpha-fetoprotein multiples of the median were found for the women who were treated with protease inhibitors compared with the women who were not (0.97 +/- 0.32 [SD] MoM vs 1.2 +/- 0.4 MoM, respectively; P = .04). Six of 39 women (15%) had positive maternal serum screens. All the babies were normal at birth, and there were no cases of perinatal transmission of human immunodeficiency virus. CONCLUSION: Protease inhibitors are associated with lower alpha-fetoprotein levels in women who are infected with human immunodeficiency virus.

Adult↗