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Increased hepatic glucose output and decreased glucose utilization are implicated in the development of type 2 diabetes. We previously reported that the expression of a novel gene, Tanis, was upregulated in the liver during fasting in the obese/diabetic animal model Psammomys obesus. Here, we have further studied the protein and its function. Cell fractionation indicated that Tanis was localized in the plasma membrane and microsomes but not in the nucleus, mitochondria, or soluble protein fraction. Consistent with previous gene expression data, hepatic Tanis protein levels increased more significantly in diabetic P. obesus than in nondiabetic controis after fasting. We used a recombinant adenovirus to increase Tanis expression in hepatoma H4IIE cells and investigated its role in metabolism. Tanis overexpression reduced glucose uptake, basal and insulin-stimulated glycogen synthesis, and glycogen content and attenuated the suppression of PEPCK gene expression by insulin, but it did not affect insulin-stimulated insulin receptor phosphorylation or triglyceride synthesis. These results suggest that Tanis may be involved in the regulation of glucose metabolism, and increased expression of Tanis could contribute to insulin resistance in the liver., A major factor that contributes to hyperglycemia in type 2 diabetes is excessive hepatic glucose production. Depending on the concentrations of insulin and glucagon in the portal blood and the [...]

Most oral contraceptives used in the US as of 2000 do not cause abnormalities in glucose metabolism. This can be an early sign of diabetes, but no effects of oral contraceptives on glucose metabolism were found in a study of 4,120 healthy women and 70 women with diabetes.

Insulin resistance may be a factor in hypertensive disorders of pregnancy. Gestational diabetes mellitus is associated with increased risk for preeclampsia or other hypertensive disorders during pregnancy, although not at a statistically significant level. Likelihood of preeclampsia also is positively correlated with the plasma glucose level one hour after a 50-g oral glucose challenge. Preeclampsia was not prevented by calcium supplementation.

To examine whether impairment of intracellular glucose metabolism precedes insulin resistance, we determined the time courses of changes in insulin-stimulated glucose uptake, glycolysis, and glycogen synthesis during high-fat feeding in [...]

Abnormalities in extracellular matrix degradation may play a pathogenetic role in diabetic nephropathy. Cultured renal mesangial cells are known to synthesize increased amounts of matrix proteins when incubated in high [...]

Women who had gestational diabetes during pregnancy may be likely to have glucose intolerance in the early postpartum weeks, especially if they required insulin therapy during pregnancy. A group of 145 women who had gestational diabetes, 74% of whom were black, had an oral glucose tolerance test five to 10 weeks after the birth. Ten percent tested as diabetics and an additional 5% showed impaired glucose tolerance. Maternal age, race, and obesity did not predict glucose intolerance, but the need for insulin therapy during pregnancy did. Five percent of gestational diabetics controlled by diet were glucose intolerant after birth versus 30% of those who required insulin. All women testing as diabetics in the postpartum period required insulin therapy during the pregnancy.

Positron-emission tomography (PET) measures differences in cerebral blood flow (CBF) of different regions of the brain, by assessing glucose metabolism. The signal measured in PET derives from the decay of injected or inhaled radioactive substances such as carbon-11 and fluorine-18. Unlike computerized tomography (CT), which measures brain structures, PET measures brain function. Studies of normal aging processes using PET have shown an age-related decline in gray matter CBF. However, in Alzheimer's disease (AD) this decline seems to be progressive. In AD, a continuing decline in the rate of oxygen metabolism of both gray and white matter has also been demonstrated. These declines have been shown to be related to the severity of cognitive impairment. In multi-infarct dementia (MID) - a dementia in which brain tissue death is related to impaired blood flow - PET scans demonstrate global reductions in cerebral metabolism. Multiple lesions in the cortex, subcortical white matter and cerebellum have also been shown in MID. The majority of patients with mental illness such as schizophrenia or manic-depressive psychosis have brains which appear to be structurally normal, suggesting the importance of the role of functional abnormalities in psychiatric disorders. However, PET studies of schizophrenia have yielded inconsistent and inconclusive results, and have failed to point to any specific marker dysfunctions. Comparatively few studies have been carried out with PET on patients with major affective (mood) disorders. While PET is potentially the most powerful noninvasive technique available for investigating brain function, finer-grained diagnostic analysis will not be possible until methodological procedures across studies are refined and standardized. (Consumer Summary produced by Reliance Medical Information, Inc.)

Substances needed for metabolic reactions (fuels) reach the fetus in proportion to their concentration in the mother's body, for the most part: thus, fetal nutrition is intimately coupled to maternal metabolism. Since fetal cells are particularly sensitive to changes in the immediate chemical environment, it is possible that neonatal behavior could be affected by the substances to which the fetus was exposed in utero. To evaluate the effects of different metabolic profiles on neonatal behavior, 209 pregnant women and their babies were studied. Seventy-three were diabetic before they became pregnant (pregestational diabetes); 112 had developed gestational diabetes (abnormal glucose metabolism beginning in pregnancy); and 24 had no abnormalities of carbohydrate metabolism. A multidisciplinary team provided prenatal care, which included regular assessment of the levels of glucose, hemoglobin AIC (HbAIC; levels rise when diabetes is poorly regulated), and beta-hydroxybutyrate, also associated with poorly regulated glucose levels. The mothers' health was maintained optimally, with careful blood glucose control, and the group ultimately had low perinatal mortality. Infants were evaluated according to the Brazelton neonatal behavioral assessment scale, which assesses them along four dimensions: interactive, motoric, state control, and physiologic control. Results showed that the women with pregestational diabetes had infants with a lower gestational age at delivery than women in the other two groups, and both diabetic groups had heavier babies than the nondiabetic group. Differences among the groups were found with respect to metabolic variables, mainly in ways that could be anticipated from their physiological characteristics. Of greatest significance was the fact that three of the four Brazelton scores were correlated with the extent of prenatal maternal glucose regulation. Women with poorer control had neonates whose assessment scores were poorer for the interactive, motoric, and physiologic control dimensions. These differences were not the result of ethnic or economic differences. The results support the hypothesis that maternal fuels influence the fetal phenotype; that differences were found among groups of well-controlled, only moderately affected, diabetic mothers, indicates how sensitive developmental variables are to such effects. (Consumer Summary produced by Reliance Medical Information, Inc.)

In insulin-dependent diabetes mellitus (IDDM), the insulin-secreting beta-cells of the pancreas degenerate, leading to elevated blood glucose levels. Patients suffering from IDDM have, among other consequences of the disease, an increased frequency of stroke and a poorer prognosis for recovery from stroke (interruption of blood flow within the brain caused by bleeding or blockage). In animal experiments using chemically-induced diabetes, diabetic rats were found to have a different response to transient ischemia (temporary reduction of the blood supply to the brain) than normal rats. To further investigate this phenomenon, rats were made diabetic by injection of the beta-cell toxin streptozocin (ST) and, after either two days or four months of diabetes, glucose metabolism and blood flow in several different brain regions were evaluated. After two days, three brain regions (the neocortex, basal ganglia, and white matter) showed an increase (from 8 to 37 percent) in glucose metabolism, with no change in blood flow. After four months, these same three regions showed a decrease (from 30 to 60 percent) in glucose metabolism with small, nonsignificant decreases in blood flow. The initial increase in glucose metabolism in ST-treated rats is unexplained, but may be a direct effect of the ST on brain function. The delayed decrease in glucose metabolism is thought to reflect the metabolic shift that occurs in untreated IDDM, whereby glucose is partially replaced by fat metabolites (ketone bodies) as the preferred source of energy for the brain. Previously reported results on the electrical activity of brain cells in diabetic rats are consistent with these metabolic shifts. (Consumer Summary produced by Reliance Medical Information, Inc.)

In healthy people, normal blood glucose (sugar) concentrations are maintained by a balance between uptake of glucose by body tissues (using insulin) and release of glucose into the blood by the liver. Both uptake and release of glucose require that glucose be transported across the cell membrane, and a recently recognized class of proteins called glucose transporters (GTs) has been shown to mediate this transport. Different types of GTs have been described, some of which increase their activity in response to insulin, and some of which do not. In insulin-dependent diabetes mellitus (IDDM), the insulin-producing beta-cells of the pancreas are destroyed, with a subsequent failure to regulate blood glucose levels. Glucose metabolism in many tissues is markedly altered in IDDM. Output of glucose by the liver is increased in insulin-deficient conditions. Recent studies have shown that GTs in fat cells are decreased in the diabetic state, but the effect of diabetes on liver GTs has not been investigated. Rats were rendered diabetic with a single injection of streptozocin, which is toxic to the beta-cells. They were maintained for 10 days in the diabetic state, and then for an additional five days either with or without insulin replacement therapy. Levels of liver GTs and an index of the synthesis of liver GTs (GT mRNA levels) were measured. Diabetes caused an increase in liver GT and GT mRNA levels, which was attenuated by insulin replacement therapy. This is in contrast to the levels of GTs and GT mRNA in fat cells, which are decreased in diabetes. These alterations in liver GT levels may be responsible for the increased output of glucose by the liver that is seen in diabetes. (Consumer Summary produced by Reliance Medical Information, Inc.)

ROBERT D. LINDEMAN, MD [1,2] LINDA J. ROMERO, MD [2,3] ASENATH LARUE, PHD [2,4] C. LILLIAN YAU, MS [2] DAVID S. SCHADE, MD [1] KATHLEEN M. KOEHLER, PHD [2] RICHARD [...]

IRINA KOWALSKA, MD [1] JOLANTA PROKOP, MD [2] HANNA BACHORZEWSKA-GAJEWSKA, MD [2] BEATA TELEJKO, MD [1] IDA KINALSKAL, MD [1] WACLAW KOCHMAN, MD [3] WLODZIMIERZ MUSIAL, MD [2] Postload glycemia [...]

JIMMY P.S. CHERN, MD [1] KAI-HSIN LIN, MD [2] MENG-YAO LU, MD [2] DONG-TSAM LIN, MD [2] KUO-SIN LIN, MD, PHD [2] JONG-DAR CHEN, MD [1] CHENG-CHUNG FU, MD [1] [...]

2001 FEB 24 - (NewsRx.com) -- Fat cells that can't take up blood sugar normally appear to trigger the same problem in muscle and a related problem in liver, say [...]

The presence of tumors places rigorous metabolic demands on the host and the growing tumor poses a stress on the host to maintain normal blood glucose levels. Hepatic glucose-6-phosphatase (G6Pase) [...]

We sought to determine if variation in genes influencing insulin action and/or secretion contribute to the high prevalence of glucose intolerance in women with polycystic ovary syndrome (PCOS) and their [...]

To directly assess the role of ATP-sensitive K ([K.sub.ATP]) channel in glucosestimulated insulin secretion we made and characterized type 1 sulfonylurea receptor (Sur1) knock-out (Sur1 KO) mice. Formation of functional [...]

Hyperglycemia of diabetes, is caused in part by perturbation of hepatic glucose metabolism. Hepatic glucokinase (GK) is an important regulator of glucose storage and disposal in the liver. This project [...]

Brain glycogen is an endogenous store of carbohydrates that can serve as a fuel during hypoglycemia. In most tissues, glycogen (Glyc) has been shown to replete to levels higher than [...]

The increased risk of hypoglycemia during intensified treatment of type 1 diabetes (T1DM) is attributed to suppressed adrenomedullary responses. A consequence of this impairment of catecholamine secretion might be reduced [...]

Salicylate treatment has previously been demonstrated to improve oral glucose tolerance in diabetic rats and humans. In order to examine the mechanism by which this occurs, insulin-stimulated glucose metabolism and [...]

The current WHO diagnostic criteria for diabetes mellitus (DM) and other categories of hyperglycemia classify abnormal glucose tolerance according to elevated blood glucose concentrations in either the fasting or postload [...]

Background: The role of gluconeogenesis from protein in the pathogenesis of weight loss in lung cancer is unclear. Objective: Our aim was to study gluconeogenesis from alanine in lung cancer patients and to analyze its relation to the degree of weight loss. Design: In this cross-sectional study, we used primed-constant infusions of [6,6-[sup.2][H.sub.2]]-D-glucose and [3-[sup.13]C]-L-alanine to assess whole-body glucose and alanine turnover and gluconeogenesis from alanine in weight-losing (WL, n = 9) and weight-stable (WS, n = 10) lung cancer patients and healthy control (n = 15) subjects. Results: Energy intake and plasma alanine concentrations did not differ significantly among the subject groups. Mean ([+ or -] SEM) whole-body glucose production was significantly higher in WL than in WS and control subjects (0.74 [+ or -] 0.06 compared with 0.55 [+ or -] 0.04 and 0.51 [+ or -] 0.04 mmol [multiplied by] [kg.sup.-1] [multiplied by] [h.sup.-1], respectively, P [is less than] 0.01). Alanine turnover was significantly elevated in WL compared with WS and control subjects (0.57 [+ or -] 0.04 compared with 0.42 [+ or -] 0.05 and 0.40 [+ or -] 0.03 mmol [multiplied by] [kg.sup.-1] [multiplied by] [h.sup.-1], respectively, P [is less than] 0.01). Gluconeogenesis from alanine was significantly higher in WL than in WS and control subjects (0.47 [+ or -] 0.04 compared with 0.31 [+ or -] 0.04 and 0.29 [+ or -] 0.04 mmol [multiplied by] [kg.sup.-1] [multiplied by] [h.sup.-1], respectively, P [is less than] 0.01). The degree of weight loss was positively correlated with glucose and alanine turnover and with gluconeogenesis from alanine (r = 0.45 for all, P [is less than] 0.01). Conclusions: Aberrant glucose and alanine metabolism occurred in WL lung cancer patients. These changes were related to the degree of weight loss and not to the presence of lung cancer per se. Am J Clin Nutr 2000;71:583-9. KEY WORDS Weight loss, gluconeogenesis, alanine, lung cancer, stable isotope tracer, humans, liver, glucose metabolism, alanine metabolism, cachexia

There is a relationship between the rate at which the 'grey matter' of the brain, the front main folded surface part (the cortex), consumes sugar (glucose) and damage to a certain part of the brain beneath this part (the nucleus basalis of Meynert). A few days after damage on one side of the brain to the nucleus basalis, both sides of the grey matter of the brain consume significantly less sugar, but sugar consumption returns to normal over a few months. In certain parts (frontal, temporal, and parietal lobes) of the brain on the side that is damaged, there is a decrease in production of a substance (choline acetyltransferase) which facilitates transmission of nerve impulses. The less the brain is damaged, the smaller the drop in production of this substance and in consumption of sugar. The reason both sides of the brain consume less sugar while only one side produces less of the acetyltransferase enzyme is probably because damage to one side reduces the number of tasks the brain as a whole attempts to perform. The nerves of the brain eventually adjust to their damaged condition and start to work normally again. This may all be relevant to similar brain malfunctions that occur in Alzheimer's disease.