Kidney, glucose

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

In an attempt to conserve sodium, the kidney secretes renin increased plasma renin activity increases the release of aldosterone, which regulates the absorption of potassium and leads to kafluresis and hypokalemia. Hypokalemia is responsible in part for decreased glucose intolerance (82). Hyponatremia, postural hypotension, and pre-renal azotemia are considered of tittle consequence. Hypemricemia and hypercalcemia are not unusual, but are not considered harmful. However, hypokalemia, progressive decreased glucose tolerance, and increased semm cholesterol [57-88-5] levels are considered... 

The complex thioamide lolrestat (8) is an inhibitor of aldose reductase. This enzyme catalyzes the reduction of glucose to sorbitol. The enzyme is not very active, but in diabetic individuals where blood glucose levels can. spike to quite high levels in tissues where insulin is not required for glucose uptake (nerve, kidney, retina and lens) sorbitol is formed by the action of aldose reductase and contributes to diabetic complications very prominent among which are eye problems (diabetic retinopathy). Tolrestat is intended for oral administration to prevent this. One of its syntheses proceeds by conversion of 6-methoxy-5-(trifluoroniethyl)naphthalene-l-carboxyl-ic acid (6) to its acid chloride followed by carboxamide formation (7) with methyl N-methyl sarcosinate. Reaction of amide 7 with phosphorous pentasulfide produces the methyl ester thioamide which, on treatment with KOH, hydrolyzes to tolrestat (8) 2[. 

Sodium-dependent glucose cotransporters (SGLT) are located on small-intestine and kidney brush-border membranes. SGLT1, SGLT2, and SGLT3 are... 

GLUT2 is a glucose/fructose transport facilitator expressed in liver, small intestine, kidney, and pancreatic p-cells. GLUT2 has low-affinity for glucose (Km= 60 mM) and fructose (ivm=65 mM), and is an essential part of the glucose sensor of pancreatic (3-cells which controls insulin secretion and biosynthesis. 

Diabetes mellitus is a complicated, chronic disorder characterized by either insufficient insulin production by the beta cells of die pancreas or by cellular resistance to insulin. Insulin insufficiency results in elevated blood glucose levels, or hyperglycemia As a result of the disease, individuals with diabetes are at greater risk for a number of disorders, including myocardial infarction, cerebrovascular accident (stroke), blindness, kidney disease, and lower limb amputations. 

The conversion of glucose 6-phosphate to glucose is catalyzed by gluco e-6-pho phatase. It is ptesent in hver and kidney but absent from muscle and adipose tissue, which, therefore, cannot expott glucose into the bloodstream. 

Facilita GLUT1 ive bidirectionai transporters Brain, kidney, colon, placenta, erythrocyte Uptake of glucose... 

GLUT 2 Liver, pancreatic B cell, small intestine, kidney Rapid uptake and release of glucose... 

Sodium SGLTl -dependent unidirectionai transporter Small intestine and kidney Active uptake of glucose from lumen of intestine and reabsorption of glucose in proximal tubule of kidney against a concentration gradient... 

In the rare hereditary disease essential pentosuria, considerable quantities of L-xylulose appear in the urine because of absence of the enzyme necessary to reduce L-xylulose to xyhtol. Parenteral administration of xylitol may lead to oxalosis, involving calcium oxalate deposition in brain and kidneys (Figure 20-4). Various drugs markedly increase the rate at which glucose enters the... 

Kidney Excretion and glu-coneogenesis Gluconeogenesis Free fatty acids, lactate, glycerol Glucose Glycerol kinase, phosphoenolpyruvate carboxy kinase... 

Major amino acids emanating from muscle are alanine (destined mainly for gluconeogenesis in liver and forming part of the glucose-alanine cycle) and glutamine (destined mainly for the gut and kidneys). 

A summary of the properties of the different types of dextrans available is presented in Table 25.1. Dextrans for clinical use as plasma expanders must have moleeular weights between 40000 (= 220 glucose units) and 300000. Polymers below the minimum are excreted too rapidly fiom the kidneys, whilst those above the maximum are potentially dangerous because of retention in the body. In practice, infusions containing dextrans of average molecular weights of40000,70000 and 110000 are commonly encountered. 

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