Lipid Metabolism and Cardiometabolic Disease

Metabolic diseases such as diabetes, steatohepatitis, and coronary artery disease result from the delivery of nutrients that exceed a tissue’s energetic needs or storage capacity. The excess nutrients give rise to deleterious lipid species that impair cellular function. Summers and colleagues found that ceramides, a class of sphingolipids, alter the metabolism of liver and adipose tissue in a way that gives rise to cardiometabolic disease. Continue reading → Lipid Metabolism and Cardiometabolic Disease

How Cells Choose to Create Energy

To supply their energy needs, cells typically choose between utilizing glucose in the cytoplasm (aerobic glycolysis and lactic acid fermentation) or “burning” pyruvate in the mitochondria (mitochondrial carbohydrate oxidation). Although this is arguably the most fundamental metabolic decision that cells make, before 2012 it was not clear how cells import pyruvate into mitochondria to fuel ATP production. Continue reading → How Cells Choose to Create Energy

How Iron Deficiency Impairs Pancreatic β-Cell Function

Research in the lab of Elizabeth Leibold, PhD, showed that in mice with iron deficiency, proinsulin processing to mature insulin was impaired, resulting in reduced levels of circulating and glucose intolerance. Mice treated with iron restored insulin to normal levels and eliminated the glucose intolerance. Continue reading → How Iron Deficiency Impairs Pancreatic β-Cell Function

Biological Consequences of Reduced Energy Flux and Inefficient Energy Generation

Energy transfer processes are never perfectly efficient. Funai and colleagues have discovered that the degree of inefficiency in cellular energy exchange, particularly during oxidative phosphorylation, has important biological implications. Continue reading → Biological Consequences of Reduced Energy Flux and Inefficient Energy Generation

Commensal Microbes That Help Prevent Metabolic Disease

Our intestines are colonized by a vast consortium of bacteria, viruses, and fungi that we now know have essential influences on gut health. Research in the Round lab has recently shown that intestinal antibody responses select for specific organisms within the gut that prevent metabolic disease by limiting fat absorption within the intestine. Continue reading → Commensal Microbes That Help Prevent Metabolic Disease

Fast-acting Insulins from Cone Snails

Faster acting human insulins are needed to improve the efficacy of diabetic insulin pumps. Over the past few years, collaborating teams led by Olivera, Safavi-Hemami, Schlegel, Yandell, and Chou have made the remarkable discovery that fish-hunting cone snails use fast-acting insulins to inactivate their prey by inducing hypoglycemia. Continue reading → Fast-acting Insulins from Cone Snails

Sensing and Regulating Cellular Energy Production

Cells must decide when to expand mitochondrial capacity to accommodate increased energy demands. Rutter, Winge, and colleagues have shown that the ancient mitochondrial fatty acid synthesis system has a profound and unexpected regulatory role in driving mitochondrial biogenesis. Continue reading → Sensing and Regulating Cellular Energy Production

Neural and Cardiac Responses to Hypoglycemia

The laboratories of Simon Fisher, MD, Owen Chan, PhD, and Candace Reno, PhD, demonstrated that brain glucose sensing was impaired in rats with recurrent hypoglycemia as a result of defective glucose and lactate metabolism within the neurons and astrocytes in the hypothalamus. The resultant abnormal release of neurotransmitters—such as GABA, glutamate and dopamine—led to inadequate activation of hormonal responses to hypoglycemia. Continue reading → Neural and Cardiac Responses to Hypoglycemia