Glucose suppression

BOX 50-1 Protocol for Glucose Suppression of Growth Hormone Test... 

Serum IGF-I concentrations are elevated in active acromegaly (Figure 50-5). IGF-I concentrations often correlate better with the chnical severity of acromegaly than with glucose-suppressed or basal GH concentrations. ... 

Earll JM, Sparks LL, Forsham PH. Glucose suppression of serum growth hormone in the diagnosis of acromegaly. JAMA 1967 20T.628-30,... 

Even though intraperitoneal injection of glucose suppressed Mn-SOD activity in the rat brain and heart (K2), unlike Cu,Zn-SOD, Mn-SOD did not undergo inactivation reaction due to glycation reactions. 

The suppression test used to demonstrate the autonomous hypersecretion of GH involves giving the patient an oral glucose load and, subsequently, measuring GH levels. A sudden rise in blood glucose suppresses serum GH to 2 ng/mL or less in normal subjects, but not in patients with active acromegaly. 

The report that cAMP relieves glucose repression of iV-acetylkanamycin amidohydrolase in Streptomyces kanamyceticus, a prokaryote ( ), indicates that the repression mechanism resembles that of different catabolic enzymes in bacteria, which proceed via the inhibition of adenylate cyclase, the enzyme that converts ATP to cAMP (D 10.4). As a consequence the concentration of cAMP decreases and the transcription by RNA polymerase of operons subjected to cAMP control is inhibited (catabolite repression). In eucaryotes, however, catabolite repression could not be demonstrated. In Penicillium cyclopium for instance, glucose suppression of benzodiazepine alkaloid biosynthesis cannot be overcome by administration of cAMP or cAMP derivatives. 

It is of interest that glucose suppression of alkaloid metabolism in P. cyclopium (D 8.4.2) can be at least partially blocked by the morphological organization of the mycelium. In mycelial mats growing at the surface of solid or liquid media, i.e., under natural growth conditions, cell specialization, as indicated by alkaloid production and conidiospore formation, is suppressed by administration of high glucose concentrations. This is because only one side of the mat has contact with the medium which slows the permeation of nutrients to the other cells. 

Chatterjee, S., Vining, L. C., 1982b, Glucose suppression of 3-glucosidase activity in chloramphenicol - producing strain of Streptomyces venezuelae. Can. J. Microbiol. 28 593. 

Metformin restrains hepatic glucose production principally by suppression of gluconeogenesis. The mechanisms involve potentiation of insulin action and decreased hepatic extraction of certain gluconeogenic substrates such as lactate. In addition, metformin reduces the rate of hepatic glycogenolysis and decreases the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake and glycogenesis by skeletal muscle is increased by metformin mainly by increased... 

Antidiabetic Drugs other than Insulin. Figure 3 The antihyperglycaemic effect of metformin involves enhanced insulin-mediated suppression of hepatic glucose production and muscle glucose uptake. Metformin also exerts non-insulin-dependent effects on these tissues, including reduced fatty acid oxidation and increased anaerobic glucose metabolism by the intestine. FA, fatty acid f, increase i decrease. 

In clinical studies, selective DPP-4 inhibition increased active circulating concentrations of GLP-1 and GEP by two- to threefold. This was associated with increased glucose-induced insulin secretion and suppression of glucagon secretion, although changes in satiety and gastric emptying have not been repotted. 

Insulin resistance occurs when the normal response to a given amount of insulin is reduced. Resistance of liver to the effects of insulin results in inadequate suppression of hepatic glucose production insulin resistance of skeletal muscle reduces the amount of glucose taken out of the circulation into skeletal muscle for storage and insulin resistance of adipose tissue results in impaired suppression of lipolysis and increased levels of free fatty acids. Therefore, insulin resistance is associated with a cluster of metabolic abnormalities including elevated blood glucose levels, abnormal blood lipid profile (dyslipidemia), hypertension, and increased expression of inflammatory markers (inflammation). Insulin resistance and this cluster of metabolic abnormalities is strongly associated with obesity, predominantly abdominal (visceral) obesity, and physical inactivity and increased risk for type 2 diabetes, cardiovascular and renal disease, as well as some forms of cancer. In addition to obesity, other situations in which insulin resistance occurs includes... 

The presence of glucose may suppress degradation of a recalcitrant compound ... 

DPP-4 is a serine protease that inactivates GLP-1. GLP-1 stimulates insulin secretion and suppresses glucagon release. The inhibition of DPP-4 prolongs the half-life of GLP-1 and brings about beneficial effects on glucose levels and glucose tolerance in type 2 diabetics. Backes et al. [64] report on the parallel optimization of enzyme binding affinity and inhibition, selectivity, ADME properties, and PK (Scheme 19). 

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