Biomedical subjects

Mark Heiman

Publications and source records attributed to Mark Heiman.

5 recordsLinked to original sources

PubMed2005

Leptin: structure, function and biology.

Leptin is an adipocyte-derived hormone that acts as a major regulator for food intake and energy homeostasis. Leptin deficiency or resistance can result in profound obesity, diabetes, and infertility in humans. Since its discovery, our understanding of leptin's biological functions has expanded from anti-obesity to broad effects on reproduction, hematopoiesis, angiogenesis, blood pressure, bone mass, lymphoid organ homeostasis, and T lymphocyte systems. Leptin orchestrates complex biological effects through its receptors, expressed both centrally and peripherally. Leptin receptor belongs to the class I cytokine receptor superfamily. At least five isoforms of leptin receptor exist, primarily because of alternate splicing. The longest form is capable of full signal transduction. The short forms may serve as leptin binding proteins and play a role in leptin transporting across the blood-brain barrier. In this review, we present the crystal structure of leptin and the structural comparison with other four-helical cytokines, discuss the leptin-receptor binding models based on other cytokine-receptor complex structures, and summarize the most recent progress on leptin signal transduction pathways--especially its link to peripheral lipid metabolism through AMP-activated protein kinase and hepatic stearoyl-CoA desaturase-1 pathways. Furthermore, we propose the structure based design of leptin analogs with increased stability, improved potency, enhanced blood-brain barrier transport, and extended time action for future therapeutic application.

AMP-Activated Protein Kinase Kinases↗

PubMed2004

Three dimensional reconstruction of CT scan images to aid the cardiac surgeon.

Minimally invasive techniques and approaches have the potential advantages of less operative stress and healthcare resource utilization but at the "cost" of less operative field of view. Newer imaging techniques utilizing three dimensional reconstruction of computed tomography scan images (3DCT) can aid the cardiac surgeon in visualizing the geometric relationships to plan and execute complex surgical procedures via minimally invasive or standard approaches. Multidetector-row CT scanning and post-processing yield these 3DCT images. We describe representative examples of this imaging technology in planning complex surgical procedures. Vascular structures, pulmonary and atrial venous relationships and cardiac ventricular functional anatomy are all visualized. Utilizing advances in imaging should allow surgeons to rapidly adopt newer technologies and minimally invasive techniques.

Arteries↗

PubMed2004

Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women.

Previous studies indicate that leptin secretion is regulated by insulin-mediated glucose metabolism. Because fructose, unlike glucose, does not stimulate insulin secretion, we hypothesized that meals high in fructose would result in lower leptin concentrations than meals containing the same amount of glucose. Blood samples were collected every 30-60 min for 24 h from 12 normal-weight women on 2 randomized days during which the subjects consumed three meals containing 55, 30, and 15% of total kilocalories as carbohydrate, fat, and protein, respectively, with 30% of kilocalories as either a fructose-sweetened [high fructose (HFr)] or glucose-sweetened [high glucose (HGl)] beverage. Meals were isocaloric in the two treatments. Postprandial glycemic excursions were reduced by 66 +/- 12%, and insulin responses were 65 +/- 5% lower (both P < 0.001) during HFr consumption. The area under the curve for leptin during the first 12 h (-33 +/- 7%; P < 0.005), the entire 24 h (-21 +/- 8%; P < 0.02), and the diurnal amplitude (peak - nadir) (24 +/- 6%; P < 0.0025) were reduced on the HFr day compared with the HGl day. In addition, circulating levels of the orexigenic gastroenteric hormone, ghrelin, were suppressed by approximately 30% 1-2 h after ingestion of each HGl meal (P < 0.01), but postprandial suppression of ghrelin was significantly less pronounced after HFr meals (P < 0.05 vs. HGl). Consumption of HFr meals produced a rapid and prolonged elevation of plasma triglycerides compared with the HGl day (P < 0.005). Because insulin and leptin, and possibly ghrelin, function as key signals to the central nervous system in the long-term regulation of energy balance, decreases of circulating insulin and leptin and increased ghrelin concentrations, as demonstrated in this study, could lead to increased caloric intake and ultimately contribute to weight gain and obesity during chronic consumption of diets high in fructose.

Adult↗

PubMed2003

Elevated umbilical cord ghrelin concentrations in small for gestational age neonates.

Ghrelin has orexigenic effects. It is present in umbilical cord plasma in full-term neonates, raising the prospect that ghrelin plays a role in fetal and neonatal energy balance. We measured ghrelin in small (SGA), appropriate (AGA), and large (LGA) for gestational age neonates and evaluated whether ghrelin levels are modulated by neonatal insulin and glucose concentrations. Plasma concentrations of ghrelin, insulin, and glucose were measured in cord blood sampled at birth in 123 SGA, AGA, and LGA neonates (gestational age, 24-41 wk) born to mothers with and without diabetes. Ghrelin was detected in samples from all infants. Its concentration was 40% higher in SGA neonates (mean +/- SD, 2436 +/- 657 pg/ml) compared with AGA (1738 +/- 380) and LGA (1723 +/- 269) neonates. There was a positive correlation between ghrelin and gestational age in AGA/LGA (r = 0.23; P < 0.05) and a negative correlation in SGA (r = -0.67; P < 0.005) neonates. Therefore, the difference in ghrelin between SGA and AGA/LGA neonates decreases with advancing gestational age. Birth weight z-score, maternal hypertension, and glucose concentrations were significant determinants of ghrelin concentrations. In conclusion, SGA neonates present with higher umbilical cord ghrelin plasma concentrations than AGA/LGA neonates. Ghrelin may play a physiological role in fetal adaptation to intrauterine malnutrition.

Anthropometry↗

PubMed2002

Neuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity.

Ghrelin, a 28-amino acid acylated peptide predominantly produced by the stomach, displays strong growth hormone (GH)-releasing activity mediated by the hypothalamus-pituitary GH secretagogue (GHS)-receptors specific for synthetic GHS. The discovery of ghrelin definitely changes our understanding of GH regulation but it is also already clear that ghrelin is much more than simply a natural GHS. Ghrelin acts also on other central and peripheral receptors and shows other actions including stimulation of lactotroph and corticotroph secretion, orexia, influence on gastro-entero-pancreatic functions, metabolic, cardiovascular and anti-proliferative effects. GHS were born more than 20 years ago as synthetic molecules suggesting the option that GH deficiency could be treated by orally active GHS as an alternative to recombinant human GH (rhGH). Up to now, this has not been the case and also their usefulness as anabolic anti-aging intervention restoring GH/insulin-like growth factor-I axis in somatopause is still unclear. We are now confronted with the theoretical possibility that GHS analogues could become candidate drugs for treatment of pathophysiological conditions in internal medicine totally unrelated to disorders of GH secretion. Particularly, GHS receptor agonists or antagonists acting on appetite could represent new drug intervention in eating disorders.

Animals↗