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Clinical Gems

Our clinical gems come from the top selling medical books, and text books because knowledge is everything when it comes to diabetes.

International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #78: Insulin Actions In Vivo: Glucose Metabolism Part 4 of 9

Glucose disposal: In the basal state, steady/near steady-state conditions prevail and whole-body glucose disposal equals endogenous (hepatic) plus renal glucose production. Data on the individual contribution of organs and tissues to total glucose uptake have been obtained in regional catheterization studies. In the case of the splanchnic area, in which glucose uptake and production both occur simultaneously, such data have been derived from the combined use of glucose tracers and indwelling catheters.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #77: Insulin Actions In Vivo: Glucose Metabolism Part 3 of 9

By convention, the basal state is the metabolic condition prevailing in the morning after an overnight (10–14h) fast. This time marks the end of the longest period of fasting in ordinary life and also is the most common point of clinical observation and physiologic measurements. The true value of basal endogenous (liver plus kidney) glucose production is the one that would be reproducibly measured with the use of an irreversible glucose tracer, which loses its label at the earliest possible intracellular step without ever getting it reincorporated into a circulating tracer molecule.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #76: Insulin Actions in Vivo: Glucose Metabolism Part 2 of 9

Glucose metabolism: Introduction. Any given concentration of glucose in plasma (and in the space in equilibrium with plasma) is the result of simultaneous release of glucose into the circulation and uptake of glucose from the bloodstream into cells. Whenever plasma glucose concentration is stable, the concurrent rates of its release and overall uptake must be equal. Glucose turnover (TR) is this rate of constant flux through its system.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #75: Insulin actions in vivo: glucose metabolism Part 1 of 9

Glucose is widespread in living organisms and, with protein and fat, completes the triad of the major metabolic fuels. To a much lesser extent than in plants, glucose also constitutes a building block for structural and enzymatic components of cells as well as the extracellular matrix. As a metabolic substrate, glucose is present in organisms essentially in its simple, monomeric form (alpha-D-glucopyranose) and as a branched polymer of alpha-glucose, namely glycogen. Disaccharides of glucose (lactose, maltose, and sucrose) are quantitatively less important. Glucose is present in plasma water at a concentration that — in a healthy adult who has fasted overnight — ranges between 3.6 and 5.5 mmol L−1 (65 – 99 mg dL−1 ).

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #74: Regulation of Glucose Metabolism in Liver Part 10 of 11

Glycolysis: Glucose-6-phosphate not used for direct glycogen synthesis can be metabolized in the glycolytic pathway. About half of the glucose taken up by liver during duodenal glucose absorption will undergo glycolysis to pyruvate. The resulting pyruvate can be used for lipogenesis and amino acid synthesis, lactate production, or cycled back to glucose-6-phosphate for indirect glycogen synthesis.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #73: Regulation of Glucose Metabolism in Liver Part 9 of 11

Glucose phosphorylation as a therapeutic target for diabetes: Early experiments using genetic overexpression of glucokinase in liver of rodent models showed promise for the protection against hyperglycemia during diabetes, spawning the development of glucokinase activators. These drugs interact with allosteric sites of glucokinase, thus promoting a conformation that exposes the catalytic domain and potentiates the activity of the enzyme.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #72: Regulation of Glucose Metabolism in Liver Part 8 of 11

Linking molecular and metabolic regulation of hepatic glucose metabolism: Cross-talk between metabolism and molecular biology is an emerging mechanism of metabolic regulation and is particularly relevant to the control glucose metabolism in liver. Some transcription factors and nuclear receptors are activated in response to metabolites. During fasting lipid metabolites are released that activate PPARα and induce the gene expression of oxidative metabolism.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #71: Regulation of Glucose Metabolism in Liver Part 7 of 11

Allosteric regulation of hexose flux is another example where the regulation of gluconeogenesis occurs by interaction with glycolytic regulation. The conversion of F-1-P to F-1,6-P2 is irreversibly catalyzed by the gluconeogenic enzyme fructose-1,6- bisphosphatase, and the opposite glycolytic reaction is irreversibly catalyzed by phosphofructokinase.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #70: Regulation of Glucose Metabolism in Liver Part 6 of 11

Acute regulation of gluconeogenesis: Prior to discovery of the transcriptional mechanisms described earlier, the control of hepatic glucose metabolism was examined in great detail on the basis of substrate, allosteric, and posttranslational modification. These factors alter gluconeogenic flux rapidly (seconds to minutes) and are a critical first response to increased glucose demand.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #69: Regulation of Glucose Metabolism in Liver Part 5 of 11

Transcriptional regulation of gluconeogenesis: The gradual shift from the fed-to-fasted state is followed closely by hormonal regulation of genes encoding PEPCK, fructose-1,6-bisphosphatase, and the glucose-6-phosphatase catalytic subunit. The transcriptional regulation of these genes remains a developing research area and its many emerging nuances cannot be completely covered here.

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