Time filter

Source Type

Omaha, NE, United States

Ching Sun G.E.,Section of Endocrinology and Metabolism | Ching Sun G.E.,Louisiana State University Health Sciences Center | Kashyap S.R.,Cleveland Clinic | Kashyap S.R.,Case Western Reserve University | Nasr C.,Cleveland Clinic
Cleveland Clinic Journal of Medicine | Year: 2014

The pathophysiology of type 2 diabetes mellitus conveys increased cancer risk, and any antidiabetic drug may alter that risk in a favorable or unfavorable way. This article discusses the links between diabetes and cancer, the different agents available for treating diabetes, and the cancer risk associated with these therapies. Source

Nimitphong H.,Section of Endocrinology and Metabolism | Nimitphong H.,Boston University | Holick M.F.,Boston University | Fried S.K.,Boston University | Lee M.-J.,Boston University
PLoS ONE | Year: 2012

1,25(OH)2D3 inhibits adipogenesis in mouse 3T3-L1 adipocytes, but little is known about its effects or local metabolism in human adipose tissue. We showed that vitamin D receptor (VDR) and 1α-hydroxylase (CYP27B1), the enzyme that activates 25(OH)D3 to 1,25(OH)2D3, were expressed in human adipose tissues, primary preadipocytes and newly-differentiated adipocytes. Preadipocytes and newly-differentiated adipocytes were responsive to 1,25(OH)2D3, as indicated by a markedly increased expression of CYP24A1, a primary VDR target. 1,25(OH)2D3 enhanced adipogenesis as determined by increased expression of adipogenic markers and triglyceride accumulation (50% to 150%). The magnitude of the effect was greater in the absence of thiazolidinediones. 1,25(OH)2D3 was equally effective when added after the removal of differentiation cocktail on day 3, but it had no effect when added only during the induction period (day 0-3), suggesting that 1,25(OH)2D3 promoted maturation. 25(OH)D3 also stimulated CYP24A1 expression and adipogenesis, most likely through its conversion to 1,25(OH)2D3. Consistent with this possibility, incubation of preadipocytes with 25(OH)D3 led to 1,25(OH)2D3 accumulation in the media. 1,25(OH)2D3 also enhanced adipogenesis in primary mouse preadipocytes. We conclude that vitamin D status may regulate human adipose tissue growth and remodeling. © 2012 Nimitphong et al. Source

Dorin R.I.,Section of Endocrinology and Metabolism | Dorin R.I.,University of New Mexico | Qualls C.R.,University of New Mexico | Torpy D.J.,Endocrine and Metabolic Unit | And 2 more authors.
Critical Care Medicine | Year: 2015

Objective: Cortisol clearance is reduced in sepsis and may contribute to the development of impaired adrenocortical function that is thought to contribute to the pathophysiology of critical illness-related corticosteroid insufficiency. We sought to assess adrenocortical function using computer-assisted numerical modeling methodology to characterize and compare maximal cortisol secretion rate and free cortisol half-life in septic shock, sepsis, and healthy control subjects. Design: Post hoc analysis of previously published total cortisol, free cortisol, corticosteroid-binding globulin, and albumin concentration data. Setting: Single academic medical center. Patients: Subjects included septic shock (n = 45), sepsis (n = 25), and healthy controls (n = 10). Interventions: IV cosyntropin (250 μg). Measurements and Main Results: Solutions for maximal cortisol secretion rate and free cortisol half-life were obtained by least squares solution of simultaneous, nonlinear differential equations that account for free cortisol appearance and elimination as well as reversible binding to corticosteroid-binding globulin and albumin. Maximal cortisol secretion rate was significantly greater in septic shock (0.83 nM/s [0.44, 1.58 nM/s] reported as median [lower quartile, upper quartile]) compared with sepsis (0.51 nM/s [0.36, 0.62 nM/s]; p = 0.007) and controls (0.49 nM/s [0.42, 0.62 nM/s]; p = 0.04). The variance of maximal cortisol secretion rate in septic shock was also greater than that of sepsis or control groups (F test, p < 0.001). Free cortisol half-life was significantly increased in septic shock (4.6 min [2.2, 6.3 min]) and sepsis (3.0 min [2.3, 4.8 min] when compared with controls (2.0 min [1.2, 2.6 min]) (both p < 0.004). Conclusions: Results obtained by numerical modeling are consistent with comparable measures obtained by the gold standard stable isotope dilution method. Septic shock is associated with generally not only higher levels but also greater variance of maximal cortisol secretion rate when compared with control and sepsis groups. Additional studies would be needed to determine whether assessment of cortisol kinetic parameters such as maximal cortisol secretion rate and free cortisol half-life is useful in the diagnosis or management of critical illness-related corticosteroid insufficiency. Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. Source

Samaropoulos X.F.,Section of Endocrinology and Metabolism | Hairston K.G.,Section of Endocrinology and Metabolism | Haffner S.M.,University of Texas at San Antonio | Lorenzo C.,University of Texas at San Antonio | And 4 more authors.
Obesity | Year: 2013

Objective: Some obese individuals appear to be protected from developing type 2 diabetes mellitus and cardiovascular disease (CVD). This has led to characterizing body size phenotypes based on cardiometabolic risk factors specifically as obese or overweight, and as metabolically healthy (MH) or metabolically abnormal (MA) based upon blood pressure, lipids, glucose homeostasis, and inflammatory parameters. The aim of this study was to measure the prevalence of and describe fat distribution across these phenotypes in a minority population. Design and Methods: Hispanic participants (N = 1054) in the IRAS Family Study were categorized into different body size phenotypes. Computed tomography (CT) abdominal scans were evaluated for measures of nonalcoholic fatty liver disease (NAFLD) and abdominal fat distribution. Statistical models adjusting for familial relationships were estimated. Results: Seventy percent (70%) of the Hispanic cohort was overweight (32%) or obese (38%). Forty-one percent (n = 138) of overweight participants and 19% (n = 74) of obese participants met criteria for MH. Adjusted analyses showed the MH phenotype was associated with lower visceral adipose tissue (VAT) and higher liver density (indicating lower fat content) in obese participants (p = 0.0005 and p = 0.0002, respectively), and lower VAT but not liver density in overweight participants (p = 0.008 and p = 0.162, respectively) compared to their MA counterparts. Odds of NAFLD were reduced in MH obese (OR = 0.34, p = 0.0007) compared to MA obese. VAT did not differ between MH obese or overweight and normal weight groups. Conclusions: These findings suggest that lower levels of visceral and liver fat, despite overall increased total body fat, may be a defining feature of MH obesity in Hispanic Americans. Copyright © 2013 The Obesity Society. Source

Kuemmerle N.B.,Dartmouth Hitchcock Medical Center | Rysman E.,Catholic University of Leuven | Lombardo P.S.,Dartmouth Hitchcock Medical Center | Flanagan A.J.,Dartmouth Hitchcock Medical Center | And 14 more authors.
Molecular Cancer Therapeutics | Year: 2011

Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, and interrupting de novo FA synthesis in model systems causes potent anticancer effects. We hypothesized that, in addition to synthesis, cancer cells may obtain preformed, diet-derived FA by uptake from the bloodstream. This would require hydrolytic release of FA from triglyceride in circulating lipoprotein particles by the secreted enzyme lipoprotein lipase (LPL), and the expression of CD36, the channel for cellular FA uptake. We find that selected breast cancer and sarcoma cells express and secrete active LPL, and all express CD36. We further show that LPL, in the presence of triglyceride-rich lipoproteins, accelerates the growth of these cells. Providing LPL to prostate cancer cells, which express low levels of the enzyme, did not augment growth, but did prevent the cytotoxic effect of FA synthesis inhibition. Moreover, LPL knockdown inhibited HeLa cell growth. In contrast to the cell lines, immunohistochemical analysis confirmed the presence of LPL and CD36 in the majority of breast, liposarcoma, and prostate tumor tissues examined (n = 181). These findings suggest that, in addition to de novo lipogenesis, cancer cells can use LPL and CD36 to acquire FA from the circulation by lipolysis, and this can fuel their growth. Interfering with dietary fat intake, lipolysis, and/or FA uptake will be necessary to target the requirement of cancer cells for FA. ©2011 AACR. Source

Discover hidden collaborations