Harpers

GLUCONEOGENESIS & CONTROL OF THE BLOOD GLUCOSE / 161hyperglycemic effect of glucagon, whose actions opposethose of insulin. Most of the endogenous glucagon(and insulin) is cleared from the circulation by the liver.Other Hormones Affect Blood GlucoseThe anterior pituitary gland secretes hormones thattend to elevate the blood glucose and therefore antagonizethe action of insulin. These are growth hormone,ACTH (corticotropin), and possibly other “diabetogenic”hormones. Growth hormone secretion is stimulatedby hypoglycemia; it decreases glucose uptake inmuscle. Some of this effect may not be direct, since itstimulates mobilization of free fatty acids from adiposetissue, which themselves inhibit glucose utilization. Theglucocorticoids (11-oxysteroids) are secreted by theadrenal cortex and increase gluconeogenesis. This is aresult of enhanced hepatic uptake of amino acids andincreased activity of aminotransferases and key enzymesof gluconeogenesis. In addition, glucocorticoids inhibitthe utilization of glucose in extrahepatic tissues. In allthese actions, glucocorticoids act in a manner antagonisticto insulin.Epinephrine is secreted by the adrenal medulla as aresult of stressful stimuli (fear, excitement, hemorrhage,hypoxia, hypoglycemia, etc) and leads to glycogenolysisin liver and muscle owing to stimulation of phosphorylasevia generation of cAMP. In muscle, glycogenolysisresults in increased glycolysis, whereas in liver glucose isthe main product leading to increase in blood glucose.meals or at night. Furthermore, premature and lowbirth-weightbabies are more susceptible to hypoglycemia,since they have little adipose tissue to generatealternative fuels such as free fatty acids or ketonebodies during the transition from fetal dependency tothe free-living state. The enzymes of gluconeogenesismay not be completely functional at this time, and theprocess is dependent on a supply of free fatty acids forenergy. Glycerol, which would normally be releasedfrom adipose tissue, is less available for gluconeogenesis.The Body’s Ability to Utilize GlucoseMay Be Ascertained by Measuring ItsGlucose ToleranceGlucose tolerance is the ability to regulate the bloodglucose concentration after the administration of a testdose of glucose (normally 1 g/kg body weight) (Figure19–6). Diabetes mellitus (type 1, or insulin-dependentdiabetes mellitus; IDDM) is characterized by decreasedglucose tolerance due to decreased secretion of insulinin response to the glucose challenge. Glucose toleranceis also impaired in type 2 diabetes mellitus (NIDDM),which is often associated with obesity and raised levelsof plasma free fatty acids and in conditions where theliver is damaged; in some infections; and in response tosome drugs. Poor glucose tolerance can also be expected15FURTHER CLINICAL ASPECTSGlucosuria Occurs When the RenalThreshold for Glucose Is ExceededWhen the blood glucose rises to relatively high levels,the kidney also exerts a regulatory effect. Glucose iscontinuously filtered by the glomeruli but is normallycompletely reabsorbed in the renal tubules by activetransport. The capacity of the tubular system to reabsorbglucose is limited to a rate of about 350 mg/min,and in hyperglycemia (as occurs in poorly controlled diabetesmellitus) the glomerular filtrate may containmore glucose than can be reabsorbed, resulting in glucosuria.Glucosuria occurs when the venous blood glucoseconcentration exceeds 9.5–10.0 mmol/L; this istermed the renal threshold for glucose.Hypoglycemia May Occur DuringPregnancy & in the NeonateDuring pregnancy, fetal glucose consumption increasesand there is a risk of maternal and possibly fetal hypoglycemia,particularly if there are long intervals betweenBlood glucose (mmol/L)10501Time (h)NormalDiabeticFigure 19–6. Glucose tolerance test. Blood glucosecurves of a normal and a diabetic individual after oraladministration of 50 g of glucose. Note the initial raisedconcentration in the diabetic. A criterion of normality isthe return of the curve to the initial value within 2 hours.2