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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The variation of endogenous insulin secretion in association with fasting plasma glucose (FPG) level and the modality of treatment was assessed using serum C-peptide levels before and after breakfast and the corrected value of 24-h urinary C-peptide (24 h-UCP) in inpatients with non-insulin-dependent diabetes mellitus. The corrected value calculated as 24 h-UCP/(urinary C-peptide to creatinine clearance (CCP/CCR) ratio in the fasting state x 10) was correlated with the sum of day-long serum C-peptide levels (r = 0.93) more closely than the measured value of 24 h-UCP (r = 0.79) in 9 patients. In 52 patients treated with diet alone, 38 with sulfonylurea and 28 with insulin, fasting serum C-peptide level did not vary with FPG level, and the increment of serum C-peptide level after breakfast and the corrected value of 24 h-UCP decreased with the rise in FPG level in each treatment. These indexes were the lowest in insulin treatment among the patients with similar FPG levels. In conclusion, 24 h-UCP was demonstrated to be able to reflect day-long endogenous insulin secretion more faithfully after the correction with the CCP/CCR ratio. It was estimated that the insulin response to breakfast and day-long insulin secretion decreased with the rise in FPG level, but basal insulin secretion was maintained over a wide range of FPG levels in each treatment. Endogenous insulin secretion seemed to be somewhat suppressed or rested by exogenous insulin in insulin-treated patients.
Diabetes Res Clin Pract 1991 Dec
PMID:Variation of endogenous insulin secretion in association with treatment status: assessment by serum C-peptide and modified urinary C-peptide. 177 9

Previous studies have indicated that rodents are relatively resistant to diet-induced obesity and that this resistance may be mediated in part by the capacity for diet-induced thermogenesis in brown adipose tissue (BAT). To test this hypothesis, we fed UCP-DTA transgenic with toxigene-mediated ablation of BAT and their control littermates a "Western diet" [21% (wt/wt) fat] or normal mouse chow [6.5% (wt/wt) fat]. The diets were begun at weaning (19 days old). At the age of 12 weeks, transgenic mice receiving the Western diet were markedly obese. The increased body weight and total body lipid content were significantly greater in transgenic mice receiving the Western diet than were the additive individual effects of Western diet (in control mice) and decreased BAT (in chow-fed mice), suggesting a synergistic interaction between diminished BAT and diet. A synergistic effect of Western diet and BAT ablation was also observed for morbid metabolic complications, such as insulin resistance, hyperglycemia, and hyperlipidemia. These metabolic changes were accompanied by increased expression of tumor necrosis factor-alpha and decreased expression of GLUT4 and beta 3-adrenergic receptor messenger RNA levels in white adipose tissue of UCP-DTA transgenic mice receiving the Western diet compared to those in the other experimental groups. As previously described, transgenic mice with diminished brown fat are hyperphagic. Of note, the degree of hyperphagia in transgenics compared to controls was similar whether the animals were fed chow or a Western diet. Thus, the synergistic effect of Western diet on obesity in transgenic mice was not mediated by a further stimulation of food intake. Overall, this study demonstrates the existence of a synergistic interaction between decreased BAT and Western diet to cause marked obesity and its accompanying disorders, such as insulin resistance and hyperlipidemia, and gives further support for the view that an important function of BAT is protection from diet-induced obesity, diabetes, and insulin resistance.
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PMID:Decreased brown fat markedly enhances susceptibility to diet-induced obesity, diabetes, and hyperlipidemia. 853 14

A mitochondrial protein called uncoupling protein (UCP1) plays an important role in generating heat and burning calories by creating a pathway that allows dissipation of the proton electrochemical gradient across the inner mitochondrial membrane in brown adipose tissue, without coupling to any other energy-consuming process. This pathway has been implicated in the regulation of body temperature, body composition and glucose metabolism. However, UCP1-containing brown adipose tissue is unlikely to be involved in weight regulation in adult large-size animals and humans living in a thermoneutral environment (one where an animal does not have to increase oxygen consumption or energy expenditure to lose or gain heat to maintain body temperature), as there is little brown adipose tissue present. We now report the discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% amino-acid identity to UCP1, and describe properties consistent with a role in diabetes and obesity. In comparison with UCP1, UCP2 has a greater effect on mitochondrial membrane potential when expressed in yeast. Compared to UCP1, the gene is widely expressed in adult human tissues, including tissues rich in macrophages, and it is upregulated in white fat in response to fat feeding. Finally, UCP2 maps to regions of human chromosome 11 and mouse chromosome 7 that have been linked to hyperinsulinaemia and obesity. Our findings suggest that UCP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli.
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PMID:Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. 905 25

Recent discoveries about the roles of 2 uncoupling proteins are changing the way we view obesity and its treatment. The author is also a coauthor of a recent Nature report that mice deficient in uncoupling protein 1 (UCP1) did not become fat, as anticipated, but lean. She found that the other uncoupling protein (UCP2) was up-regulated in the brown adipose tissue (BAT) of these mice, compensating, at least in part, for the lack of UCP1 and preventing obesity. Researchers have known for 40 years that the function of BAT is heat production. In 1978, researchers discovered UCP1, the protein responsible for this function. Subsequent investigation focused on the role of this protein in staving off obesity in animal models. In the early 1990s, surprising evidence from tissues other than BAT show that 20% to 40% of resting cellular energy expenditure is used to counter a proton leak down the electrochemical gradient across the mitochondrial inner membrane. This leak was found to be related to metabolic rate; the search for the mechanism of the leak led to the discovery of UCP2. Both uncoupling proteins have been found to act as leaks in mitochondrial inner membranes, allowing the dissipation of proton motive force. These findings could lead to new treatments for obesity and non-insulin-dependent diabetes mellitus.
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PMID:Obesity research continues to spring leaks. 925 78

Uncoupling protein (UCP1) is a transmembrane proton transporter present in the mitochondria of brown adipose tissue (BAT), a specialized tissue which functions in temperature homeostasis and energy balance (Nicholls, D. G., and Locke, R. M. (1984) Physiol. Rev. 64, 2-40; Lowell, D. D., and Flier, J. S. (1997) Annu. Rev. Med.). UCP1 mediates the thermogenesis that is characteristic of BAT by uncoupling mitochondrial oxidation of substrates from ATP synthesis. Recently, two proteins related to UCP1 have been identified and designated UCP2 (Fleury, C., et al. (1997) Nature Genetics 15, 269-272) or UCP homolog (UCPH) (Gimeno, R. E., et al. (1997) Diabetes 46, 900-906) and UCP3 (Boss, O., et al. (1997) FEBS Lett. 408, 39-42; Vidal-Puig, A., et al. (1997) Biochem. Biophys. Res. Commun. 235, 79-82). We investigated the regulation in rats of UCP3, which is expressed primarily in skeletal muscle and BAT. Expression of rat UCP3 mRNA in BAT was upregulated by in vivo treatment with triiodothyronine (T3) and by exposure to cold, suggesting that UCP3 is active in thermogenesis and energy expenditure. In skeletal muscle, UCP3 mRNA was also upregulated by T3 but, surprisingly, not by cold exposure. A hypothesis is proposed to account for this differential regulation.
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PMID:Regulation of the third member of the uncoupling protein family, UCP3, by cold and thyroid hormone. 936 14

Humans and rats tend to gain weight as they age. Leptin is one regulator of food intake and energy expenditure. To determine if the increase in adiposity with age is related to altered leptin gene expression, we assessed adiposity levels, leptin mRNA levels in epididymal and inguinal white adipose tissue (EWAT and IWAT), and uncoupling protein (UCP1) mRNA levels in interscapular brown adipose tissue (IBAT) from F344 x BN rats ages 3, 12, 18, 24, and 30 months (n = 8/age). Levels of adiposity determined by the adiposity index and the Lee index increased between ages 3 and 24 months, with a decrease at age 30 months. There were parallel increases with age in body weight, EWAT, and IWAT depot size up to age 24 months, followed by a nonsignificant decrease at age 30 months. Daily food intake was unchanged with age. In EWAT, leptin mRNA per microgram of RNA was unchanged with age, whereas in IWAT, it increased up to 24 months, then declined at 30 months. Total leptin mRNA levels in both IWAT and EWAT depots increased with age, peaking at age 24 months, and were correlated with adiposity. Serum leptin levels increased with age, also peaking at age 24 months, and were correlated with total leptin mRNA in WAT pads and adiposity. The rate of increase in serum leptin was greater than the increase in adiposity with age, suggesting contributions from both the increase in leptin expression per unit of WAT and the increase in WAT depot size. In addition, UCP1 mRNA levels in IBAT did not change with age. These data suggest that adiposity increases with age and cannot be attributed to increased food intake, impaired leptin gene expression, or decreased UCP1 mRNA level in IBAT. Furthermore, leptin gene expression in IWAT increases with age independent of increasing adiposity.
Diabetes 1997 Dec
PMID:Leptin gene expression increases with age independent of increasing adiposity in rats. 939 92

Thiazolidinediones (TZDs) are a novel class of insulin-sensitizing agents used in the treatment of NIDDM and are potent agonists for the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma). The thiazolidinedione BRL 49653 has been shown to promote the differentiation of the HIB-1B brown preadipocyte cell line and to increase rat interscapular brown adipose tissue (BAT) mass. Given the importance of brown fat in the control of energy metabolism in rodents, this may represent an important therapeutic effect of this class of compound. To date, however, no studies examining the effects of TZDs on human brown fat have been reported. In the present study, we have measured uncoupling protein 1 (UCP-1) mRNA, a specific marker for BAT, in isolated adipocytes and subcultured preadipocytes prepared from different adult human adipose tissue depots. Consistent with previous studies of adult human whole adipose tissue, UCP-1 mRNA was detectable in isolated human adipocytes prepared from all depots studied with a rank order of perirenal, omental, and subcutaneous. BRL 49653 treatment of subcultured human pre-adipocytes prepared from all depots resulted in increased levels of UCP-1 mRNA, compared with those of the vehicle-treated cells. When exposed to BRL 49653 for 5 days, preadipocytes from the human perirenal depot accumulated lipid, and a proportion of cells showed clear mitochondrial staining for UCP-1 protein by confocal microscopy. Thus, cells of the brown fat lineage were detectable in all human adipose depots studied, and cultured human pre-adipocytes, particularly from the perirenal depot, showed a marked increase in UCP-1 expression in response to thiazolidinediones. Given the role of brown adipocytes in the enhancement of energy expenditure, promotion of brown fat adipogenesis by thiazolidinediones could contribute to the beneficial effects of these drugs on insulin resistance in humans.
Diabetes 1998 Jan
PMID:Thiazolidinedione exposure increases the expression of uncoupling protein 1 in cultured human preadipocytes. 942 89

Brown adipose tissue (BAT) has the capacity for uncoupled mitochondrial respiration and is proposed to be a key site for regulating energy expenditure in rodents. To better define the role of BAT in energy homeostasis, we previously created a line of transgenic mice with deficiency of BAT (UCP promoter-driven diphtheria toxin A transgenic mice [UCP-DTA]) mice. These mice develop obesity that initially is due to decreased energy expenditure and later accompanied by hyperphagia despite increased levels of circulating leptin. In addition, the obesity of these mice is accompanied by severe insulin-resistant diabetes and hyperlipidemia. To better define the basis for leptin resistance in this model, we treated UCP-DTA mice with leptin (300 microg i.p., b.i.d.) and compared their response with that of leptin-treated ob/ob and FVB control mice (30 microg i.p., b.i.d.). Leptin treatment of FVB and ob/ob mice decreased their body weight and food intake and improved their glucose homeostasis. In contrast, tenfold higher dosages of leptin had no effect on body weight, food intake, or circulating insulin or glucose concentrations of UCP-DTA mice. Hypothalamic neuropeptide Y (NPY) mRNA expression was lower in UCP-DTA mice than in littermate control FVB mice in the fed state, and increased progressively in response to food restriction as leptin levels fell. In parallel to the levels of hypothalamic NPY, corticosterone levels were initially suppressed and rose with food restriction. Thus food intake, body weight, and insulin and glucose homeostasis of UCP-DTA mice are all extraordinarily resistant to leptin, whereas hypothalamic NPY and the hypothalamopituitary adrenal (HPA) axis may remain under leptin control. Further elucidation of the mechanisms underlying leptin resistance in UCP-DTA mice may provide valuable insights into the basis for leptin resistance in human obesity.
Diabetes 1998 Feb
PMID:Severe leptin resistance in brown fat-deficient uncoupling protein promoter-driven diphtheria toxin A mice despite suppression of hypothalamic neuropeptide Y and circulating corticosterone concentrations. 951 18

Uncoupling protein 2 (UCP2) maps to a region on distal mouse chromosome 7 that has been linked to the phenotypes of obesity and type II diabetes. We recently reported that UCP2 expression is increased by high fat feeding in adipose tissue of the A/J strain of mice, which is resistant to the development of dietary obesity. More recently, a third UCP (UCP3) was identified, which is expressed largely in skeletal muscle and brown adipose tissue. The UCP2 and UCP3 genes are located adjacent to one another on mouse chromosome 7. Thus, the roles of these UCPs in both metabolic efficiency and the linkage to obesity and diabetes syndromes is unclear. For this reason, we examined the expression of UCP2 and UCP3 in white adipose tissue and interscapular brown adipose tissue and in gastrocnemius/soleus muscle preparations from the obesity-resistant A/J and C57BL/KsJ (KsJ) strains and the obesity-prone C57BL/6J (B6) mouse strain. In both KsJ and A/J mice, UCP2 expression in white fat was increased approximately 2-fold in response to 2 weeks of a high fat diet, but there was no effect of diet on UCP2 levels in B6 mice. In skeletal muscle and in brown fat, neither UCP2 nor UCP3 expression was affected by diet in A/J, B6, or KsJ mice. However, in brown fat, we observed a 2-3-fold increase in the expression of UCP1 in response to dietary fat challenge, which may be related to diet-induced elevations in plasma leptin levels. Together, these results indicate that the consumption of a high fat diet selectively regulates UCP2 expression in white fat and UCP1 expression in brown fat and that resistance to obesity is correlated with this early, selective induction of UCP1 and UCP2 and is not associated with changes in expression of UCP3.
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PMID:Diet-induced changes in uncoupling proteins in obesity-prone and obesity-resistant strains of mice. 952 Apr 93

Continuous (4 days) intracerebroventricular leptin infusion (12 microg/day) was performed in lean rats, and its hormonometabolic effects were determined. Intracerebroventricular leptin administration did not result in leakage of the hormone into the peripheral circulation. Thus, its effects were elicited by its presence within the central nervous system. Intracerebroventricular leptin infusion produced marked decreases in food intake and body weight gain relative to vehicle-infused fed ad libitum rats. Because decreases in food intake alter hormonometabolic homeostasis, additional control rats pair-fed to the amount of food consumed by leptin-infused ones were included in the study. Intracerebroventricular leptin-infused and vehicle-infused pair-fed rats were characterized, relative to vehicle-infused ad libitum-fed animals, by decreases in body weight and insulinemia and by increases in insulin-stimulated overall glucose utilization and muscle and brown adipose tissue glucose utilization index. Brown adipose tissue uncoupling protein (UCP)1, UCP2, and UCP3 mRNA levels were markedly decreased in pair-fed animals relative to those of fed ad libitum control animals, as were liver and white adipose tissue UCP2 and muscle UCP3 mRNA levels. In marked contrast, intracerebroventricular leptin administration was accompanied by the maintenance of high UCP1, UCP2, and UCP3 expression in all these tissues. Thus, despite analogies between leptin's effects and those of pair-feeding with regard to glucose handling, their respective underlying mechanisms differ. While leptin maintains or favors energy-dissipating mechanisms (UCP1, UCP2, and UCP3), the latter are markedly depressed in pair-fed rats. This effect of leptin may prevent subsequent excessive storage processes, thereby maintaining normal body homeostasis.
Diabetes 1998 Jul
PMID:Chronic central leptin infusion enhances insulin-stimulated glucose metabolism and favors the expression of uncoupling proteins. 964 22


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