Molecular biology of mammalian glucose transporters

The oxidation of glucose represents a major source of metabolic energy for mammalian cells. However, because the plasma membrane is impermeable to polar molecules such as glucose, the cellular uptake of this important nutrient is accomplished by membrane-associated carrier proteins that bind and transfer it across the lipid bilayer. Two classes of glucose carriers have been described in mammalian cells: the Na(+)-glucose cotransporter and the facilitative glucose transporter. The Na(+)-glucose cotransporter transports glucose against its concentration gradient by coupling its uptake with the uptake of Na+ that is being transported down its concentration gradient. Facilitative glucose carriers accelerate the transport of glucose down its concentration gradient by facilitative diffusion, a form of passive transport. cDNAs have been isolated from human tissues encoding a Na(+)-glucose-cotransporter protein and five functional facilitative glucose-transporter isoforms. The Na(+)-glucose cotransporter is expressed by absorptive epithelial cells of the small intestine and is involved in the dietary uptake of glucose. The same or a related protein may be responsible for the reabsorption of glucose by the kidney. Facilitative glucose carriers are expressed by most if not all cells. The facilitative glucose-transporter isoforms have distinct tissue distributions and biochemical properties and contribute to the precise disposal of glucose under varying physiological conditions. The GLUT1 (erythrocyte) and GLUT3 (brain) facilitative glucose-transporter isoforms may be responsible for basal or constitutive glucose uptake. The GLUT2 (liver) isoform mediates the bidirectional transport of glucose by the hepatocyte and is responsible, at least in part, for the movement of glucose out of absorptive epithelial cells into the circulation in the small intestine and kidney. This isoform may also comprise part of the glucose-sensing mechanism of the insulin-producing beta-cell. The subcellular localization of the GLUT4 (muscle/fat) isoform changes in response to insulin, and this isoform is responsible for most of the insulin-stimulated uptake of glucose that occurs in muscle and adipose tissue. The GLUT5 (small intestine) facilitative glucose-transporter isoform is expressed at highest levels in the small intestine and may be involved in the transcellular transport of glucose by absorptive epithelial cells. The exon-intron organizations of the human GLUT1, GLUT2, and GLUT4 genes have been determined. In addition, the chromosomal locations of the genes encoding the Na(+)-dependent and facilitative glucose carriers have been determined. Restriction-fragment-length polymorphisms have also been identified at several of these loci.(ABSTRACT TRUNCATED AT 400 WORDS)     

Quality of diabetes care in U.S. academic medical centers: low rates of medical regimen change

OBJECTIVE: To assess both standard and novel diabetes quality measures in a national sample of U.S. academic medical centers. RESEARCH DESIGN AND METHODS: This retrospective cohort study was conducted from 10 January 2000 to 10 January 2002. It involved 30 U.S. academic medical centers, which contributed data from 44 clinics (27 primary care clinics and 17 diabetes/endocrinology clinics). For 1,765 eligible adult patients with type 1 or type 2 diabetes with at least two clinic visits in the 24 months before 10 January 2002, including one visit in the 6 months before 10 January 2002, we assessed measurement and control of HbA(1c), blood pressure, and cholesterol and corresponding medical regimen changes at the most recent clinic visit. RESULTS: In this ethnically and economically diverse cohort, annual testing rates were very high (97.4% for HbA(1c), 96.6% for blood pressure, and 87.6% for total cholesterol). Fewer patients were at HbA(1c) goal (34.0% <7.0%) or blood pressure goal (33.0% <130/80 mmHg) than lipid goals (65.1% total cholesterol <200 mg/dl, 46.1% with LDL cholesterol <100 mg/dl). Only 10.0% of the cohort met recommended goals for all three risk factors. At the most recent clinic visit, 40.4% of patients with HbA(1c) concentrations above goal underwent adjustment of their corresponding regimens. Among untreated patients, few with elevated blood pressure (10.1% with blood pressure >130/80 mmHg) or elevated LDL cholesterol (5.6% with LDL >100 mg/dl) were started on corresponding therapy. Patients with type 2 diabetes were no less likely to be intensified than patients with type 1 diabetes. CONCLUSIONS: High rates of risk factor testing do not necessarily translate to effective metabolic control. Low rates of medication adjustment among patients with levels above goal suggest a specific and novel target for quality improvement measurement.     

Leucine. A possible regulator of protein turnover in muscle.

Incorporation of radiolabeled precursors into muscle proteins was studied in isolated rat hemidiaphragms. A mixture of three branched-chain amino acids (0.3 mM each) added to media containing glucose stimulated the incorporation of [14C]lysine into proteins. When tested separately, valine was ineffective, isoleucine was inhibitory, but 0.5 mM leucine increased the specific activity of muscle proteins during incubation with [14C]lysine or [14C]acetate in hemidiaphragms from fed or fasted rats incubated with or without insulin. Preincubation with 0.5 mM leucine increased the specific activity of muscle proteins during a subsequent 30- or 60-min incubation with [14C]lysine or [14C]pyruvate without leucine. Preincubation with other amino acids (glutamate, histidine, methionine, phenylalanine, or tryptophan) did not exert this effect. When hemidiaphragms were incubated with a mixture of amino acids at concentrations found in rat serum and a [14C]lysine tracer, the specific activity of muscle proteins increased when leucine in the medium was raised from 0.1 to 0.5 mM. Experiments with actinomycin D and cycloheximide suggested that neither RNA synthesis nor protein synthesis are required for the initiation of the leucine effect. Leucine was not effective when added after 1 h preincubation without leucine. The concentration of lysine in the tissue water of diaphragms decreased during incubation with 0.5 mM leucine in the presence or absence of cycloheximide, suggesting that leucine inhibited protein degradation. During incubation with [3h]tyrosine (0.35 mM) the addition of 0.5 mM leucine increased the specific activity of muscle proteins, while the specific activity of intracellular tyrosine remained constant and its concentration decreased, suggesting that leucine also promoted protein synthesis. The concentration of leucine in muscle cells or a compartment thereof may play a role in regulating the turnover of muscle proteins and influence the transition to negative nitrogen balance during fasting, uncontrolled diabetes, and the posttraumatic state. Leucine may play a pivotal role in the protein-sparing effect of amino aicds.     

The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes

The term "metabolic syndrome" refers to a clustering of specific cardiovascular disease (CVD) risk factors whose underlying pathophysiology is thought to be related to insulin resistance. Since the term is widely used in research and clinical practice, we undertook an extensive review of the literature in relation to the syndrome's definition, underlying pathogenesis, and association with CVD and to the goals and impact of treatment. While there is no question that certain CVD risk factors are prone to cluster, we found that the metabolic syndrome has been imprecisely defined, there is a lack of certainty regarding its pathogenesis, and there is considerable doubt regarding its value as a CVD risk marker. Our analysis indicates that too much critically important information is missing to warrant its designation as a "syndrome." Until much needed research is completed, clinicians should evaluate and treat all CVD risk factors without regard to whether a patient meets the criteria for diagnosis of the "metabolic syndrome."     

Facilitating communication with patients for improved migraine outcomes

Effective communication is integral to good medical care. Medical professional groups, regulatory agencies, educators, researchers, and patients recognize its importance. Quality of medical communication is directly related to patient satisfaction, improvement in medication adherence, treatment compliance, other outcomes, decreased risk of malpractice, and increase in health care providers’ levels of satisfaction. However, skill level and training remain problematic in this area. Fortunately, research has shown that medical communication skills can be successfully taught and acquired, and that improvement in communication skills improves outcomes. The American Migraine Communication Studies I and II evaluated the current state of health care provider-patient communication in headache care and tested a simple educational intervention. They found problematic issues but demonstrated that these areas could be improved. We review theoretical models of effective communication and discuss strategies for improving communication, including active listening, interviewing strategies, and methods for gathering information about headache-related impairment, mood, and quality of life.     

Palliative und supportive Therapie des Nierenzellkarzinoms

At the time of diagnosis, 25-30% of all patients with renal cell carcinoma already present with metastatic disease. Furthermore, 20-30% of patients with renal cell carcinoma will have progressive disease despite radical nephrectomy with complete tumor resection.In this review, we discuss the current therapeutic options for patients with metastatic renal cell carcinoma: These include palliative radical nephrectomy, surgery of metastasis, tumor embolisation and medical treatment options (e.g. immunotherapy, chemotherapy and targeted therapy), as well as supportive pain treatment.