Search Results - (Author, Cooperation:R. Burcelin)

2012-06-08

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Aging ; Animals ; Bacteria/*metabolism ; Diet ; Gastrointestinal Tract/*metabolism/*microbiology ; Health ; Humans ; Immune System/physiology ; Inflammation ; Liver/metabolism ; Metabolic Diseases/metabolism/*microbiology ; *Metabolic Networks and Pathways ; *Metagenome ; Signal Transduction

1432-1440

Key words Glucose transporter 4 ; Transgenic mice ; Insulin action ; Glucose homeostasis

Springer Online Journal Archives 1860-2000

Medicine

Abstract  Glucose transporters are a family of membrane proteins which mediate glucose uptake across the cell membrane. The facilitative glucose transporter proteins are products of unique genes and are expressed in a tissue-specific manner. They are very similar structurally, containing 12 putative membrane spanning domains. Functionally they vary in their affinity for glucose and sensitivity to hormones such as insulin. Glucose homeostasis depends mainly on controlled changes in glucose transport in insulin-responsive tissues such as skeletal muscle and adipose cells where both glucose transporter 1 and glucose transporter 4 are expressed. Glucose transporter 4 is the major glucose transporter in these tissues and translocates from an intracellular vesicle to the cell membrane in response to insulin. Alterations of the level of expression of these glucose transporters should result in changes in insulin sensitivity and modification of whole-body metabolism. To test these hypotheses transgenic mouse models have been generated which overexpress glucose transporters in specific tissues or in the whole body. Glucose transporter 1 and glucose transporter 4 have been overexpressed specifically in skeletal muscle and glucose transporter 4 specifically in adipose tissue. Mice have also been made which overexpress glucose transporter 4 in the whole body. Using homologous recombination technology to disrupt the glucose transporter 4 gene, a ”knockout” mouse has been created which expresses no glucose transporter 4. The metabolic consequences of these genetic manipulations on the level of expression of glucose transporters in the mouse are reviewed. The future applications of transgenic mouse technology in creating models which mimic human diseases are also discussed.

Electronic Resource

1432-0428

Key words Streptozotocin ; insulinopenic diabetes ; glucose turnover ; gluconeogenesis ; insulin resistance

Springer Online Journal Archives 1860-2000

Medicine

Summary Glucose production and utilization and activities of key enzymes involved in liver and muscle glucose metabolism were studied in post-absorptive streptozotocin-diabetic rats after 12 h of severe hyperglycaemia (17.5 ± 0.5 mmol/l) and insulinopenia (5 ± 1 μU/ml). Basal glucose production was increased: 36.6 ± 3.0 mg · kg · min–1, vs 24.4 ± 2.5 in controls (p 〈 0.05); liver glycogen concentration was decreased by 40 % (p 〈 0.05); liver phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities were increased by 375 and 156 %, respectively (p 〈 0.001 and 〈 0.01). During a euglycaemic clamp at a plasma insulin level of 200 μU/ml, glucose production was totally suppressed in controls, but persisted at 20 % of basal in diabetic rats. In these rats, glucose production was suppressed at a plasma insulin level of 2500 μU/ml. Basal whole body glucose utilization rate, 2-deoxy-1-[3H]-d-glucose ([3H]-2dG) uptake by muscles and muscle glycogen concentrations were similar in both groups, as well as total and active forms of pyruvate dehydrogenase and glycogen synthase activities. During the euglycaemic clamp, the total body glucose utilization rates and [3H]-2dG uptake by muscles were similar in control and diabetic rats at a plasma insulin level of 200 μU/ml, but lower in diabetic rats at a plasma insulin level of 2500 μU/ml. We conclude 1) in recent-onset severely insulinopenic rats, an excessive glucose production via gluconeogenesis prevailed, mainly accounting for the concomitant hyperglycaemia. This excess glucose output cannot be attributed to liver insulin resistance: the gluconeogenic pathway is physiologically less sensitive than glycogenolysis to the inhibition by insulin. 2) Glucose utilization was apparently normal under hyperglycaemic conditions and at a lower insulin plateau of the euglycaemic clamp but suboptimal in the presence of maximal insulin concentrations, suggesting an early appearance of peripheral insulin resistance. [Diabetologia (1995) 38: 283–290]

Electronic Resource

1432-0428

Streptozotocin ; insulinopenic diabetes ; glucose turnover ; gluconeogenesis ; insulin resistance

Springer Online Journal Archives 1860-2000

Medicine

Summary Glucose production and utilization and activities of key enzymes involved in liver and muscle glucose metabolism were studied in post-absorptive streptozotocin-diabetic rats after 12 h of severe hyperglycaemia (17.5±0.5 mmol/l) and insulinopenia (5±1 ΜU/ml). Basal glucose production was increased: 36.6±3.0 mg·kg·min−1, vs 24.4±2.5 in controls (p〈0.05); liver glycogen concentration was decreased by 40% (p〈0.05); liver phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities were increased by 375 and 156%, respectively (p〈0.001 and 〈0.01). During a euglycaemic clamp at a plasma insulin level of 200 ΜU/ml, glucose production was totally suppressed in controls, but persisted at 20% of basal in diabetic rats. In these rats, glucose production was suppressed at a plasma insulin level of 2500 ΜU/ml. Basal whole body glucose utilization rate, 2-deoxy-1-[3H]-d-glucose ([3H]-2dG) uptake by muscles and muscle glycogen concentrations were similar in both groups, as well as total and active forms of pyruvate dehydrogenase and glycogen synthase activities. During the euglycaemic clamp, the total body glucose utilization rates and [3H]-2dG uptake by muscles were similar in control and diabetic rats at a plasma insulin level of 200 ΜU/ ml, but lower in diabetic rats at a plasma insulin level of 2500 ΜU/ml. We conclude 1) in recent-onset severely insulinopenic rats, an excessive glucose production via gluconeogenesis prevailed, mainly accounting for the concomitant hyperglycaemia. This excess glucose output cannot be attributed to liver insulin resistance: the gluconeogenic pathway is physiologically less sensitive than glycogenolysis to the inhibition by insulin. 2) Glucose utilization was apparently normal under hyperglycaemic conditions and at a lower insulin plateau of the euglycaemic clamp but suboptimal in the presence of maximal insulin concentrations, suggesting an early appearance of peripheral insulin resistance.

Electronic Resource