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Biomedical subjects

R K Kalkhoff

Publications and source records attributed to R K Kalkhoff.

At least 37 records · Page 2Linked to original sources
PubMed1983

Computed tomographic study of hormone-secreting microadenomas.

A review was made of the computed tomographic (CT) studies of 33 patients with hormone-secreting microadenomas that had been verified by transsphenoidal surgery and endocrinologic evaluation. In previous studies in small series of patients, the CT appearance of pituitary microadenomas has been reported as hypodense, isodense, and hyperdense. In this study, CT showed a region of diminished enhancement and usually an enlarged pituitary gland in cases of prolactin-secreting adenomas. HGH- or ACTH-secreting adenomas were less consistently hypodense. It is concluded that hypodensity and enlargement in the pituitary gland are the most useful criteria for identification of microadenomas. Some technical factors that may affect the CT appearance of microadenomas and lead to conflicting reports are discussed.

Adenoma↗
PubMed1983

Tolbutamide perifusion of rat islets. Sequential changes in calcium, phosphorus, sodium, potassium, and chlorine in single beta cells.

Fluctuations of calcium, phosphorus, sodium, potassium, and chlorine in beta cells were followed during rat islet perifusion with tolbutamide and related to insulin secretion. In 24 paired experiments two chambers containing 100 islets were perifused with buffered medium containing 4.2 mM glucose alone or with added tolbutamide (200 micrograms/ml). Effluent was collected frequently for insulin determinations. At eight different time intervals from 0 to 20 min islets were acutely fixed, prepared for scanning electron microscopy and beta cells in islet tissue were identified. Element content in 480 single cells was measured by energy dispersive x-ray analysis. Tolbutamide elicited typical monophasic insulin release that exceeded control islet secretory rates from 2 to 6 min with a peak value at 3 min. This pattern was preceded by monophasic calcium accumulation in beta cells that abruptly rose 150% above control cells at 1 min and declined to base line by 4 min. The rapid ascent of calcium was associated with significant depressions of sodium and potassium content without alterations of cell phosphorus. Chlorine fell at 2 min and then rose greater than 50% above control cells at 4 min. After 6 min insulin secretion and element content remained near control levels. We conclude that monophasic calcium accumulation in beta cells is the earliest, most predictive event of islet insulin secretion after a tolbutamide stimulus. Oscillations of beta cell sodium and potassium reciprocally relate to calcium, and an elevation of chlorine content is a relatively late phenomenon in the stimulus-secretion coupling process.

Animals↗
PubMed1983

Relative effects of pregnancy and corticosterone administration on skeletal muscle metabolism in the rat.

The effects of pregnancy and corticosterone treatment on skeletal muscle metabolism were compared using a noncyclically perfused rat hindlimb preparation. Animal groups studied included 3-week-pregnant animals, rats injected with corticosterone (7.5 mg/100 g BW . day) for 3 days, and age-matched control rats. All were fasted 24 h before perfusion. In baseline perfusions devoid of insulin, no differences were observed among the groups with respect to muscle glucose uptake and the release of lactate, pyruvate, and glycerol. Baseline alanine and phenylalanine release were significantly increased in corticosterone-treated rats compared to values observed in control and pregnant animals. In perfusions with 100 or 500 microU/ml insulin, glucose uptake was increased 5-fold above baseline uptake in the control group. At 100 microU/ml insulin concentrations, glucose uptake in pregnant and corticosterone-treated rats achieved only 50% of the increase seen in control experiments. With 500 microU/ml insulin, glucose uptake was decreased 20% in pregnant animals and 40% in rats receiving corticosterone relative to control values. Alanine release was significantly reduced below baseline after the administration of 500 microU/ml insulin in control rats. In these rats, phenylalanine release, an index of net protein degradation, also was reduced with both 100 and 500 microU/ml insulin. Similar insulin concentrations did not suppress the efflux of either amino acid below baseline in pregnant or corticosterone-treated groups. Corticosterone administration to nonpregnant rats appears to duplicate changes in skeletal muscle metabolism that occur during late rat pregnancy. Insulin resistance in both states is manifested by a decrease in insulin-stimulated glucose uptake and an inability of insulin to suppress net muscle proteolysis. Since plasma free glucocorticoid concentrations are increased in late human as well as rat gestation, these steroids may have an important role in the development of insulin resistance at skeletal muscle sites in this state.

Amino Acids↗
PubMed1983

Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopausal women.

A possible role for increased androgenic/estrogenic activity in the pathogenesis of upper body fat localization and its accompanying cellular and metabolic characteristics was examined. Eighty healthy, nonhirsute, premenopausal, caucasian women with a wide range of body fat topography [waist to hips girth ratio (WHR), 0.64 to 1.02] and obesity level (percentage of ideal body weight, 92-251%) were studied. Increasing androgenicity, as reflected by a decrease in plasma sex hormone-binding globulin capacity and an increase in the percentage of free testosterone, was accompanied by 1) increasing WHR, this relationship being independent of and additive to that of obesity level; 2) increasing size of abdominal, but not femoral, adipocytes; 3) increasing plasma glucose and insulin levels, both basally and in response to oral glucose loading; and 4) diminished in vivo insulin sensitivity, as revealed by increasing steady state plasma glucose levels at comparable plasma insulin levels, attained by the infusion of somatostatin, insulin, and glucose. No association was found between total plasma testosterone, androstenedione, dehydroepiandrosterone sulfate, or estradiol concentrations and WHR, fat cell size, or metabolic profiles. We, therefore, propose that in premenopausal women, a relative increase in tissue exposure to unbound androgens may be responsible in part for localization of fat in the upper body, enlargement of abdominal adipocytes, and the accompanying imbalance in glucose-insulin homeostasis.

Adipose Tissue↗
PubMed1983

Relationship of body fat distribution to blood pressure, carbohydrate tolerance, and plasma lipids in healthy obese women.

In 110 obese, healthy women, a relationship was sought between distribution of body fat and blood pressure, glucose tolerance, plasma insulin, and fasting plasma lipid and serum uric acid concentrations. The index of body fat distribution was the ratio of waist circumference to hips circumference (WHR). The WHR range in this group was 0.5 to 0.99, with a median value of 0.78. Positive, significant correlations were found between WHR and both systolic and diastolic blood pressure and between WHR and the total integrated plasma glucose and insulin responses during 4 hr oral glucose tolerance tests. No relationship was found between WHR and age, the degree of obesity as defined by the weight-to-height ratio, or concentrations of fasting plasma free fatty acids, plasma triglyceride, plasma cholesterol, or serum uric acid. Subsequently, 27 women in the highest quartile of the WHR range (0.83 to 0.99) were compared to 28 age- and weight-matched subjects in the lowest quartile of WHR (0.5 to 0.73). Women in the highest quartile had systolic and diastolic blood pressure as well as total plasma glucose and insulin responses during glucose tolerance tests that significantly exceeded mean values of subjects in the lowest quartile. We conclude that in healthy, obese women, a continuum exists that relates increasing fat accumulation in the upper body to progressively higher blood pressure, reduced carbohydrate tolerance, and higher plasma insulin concentrations. These changes occurred independently of age of degree of obesity in this population.

Adipose Tissue↗
PubMed1982

Metabolic effects of progesterone.

Progesterone has important effects on carbohydrate, lipid and protein metabolism. This steroid induces hyperinsulinemia, possibly by direct action on pancreatic islets, while promoting glycogen storage in the liver. Paradoxically, it antagonizes the effects of insulin on glucose metabolism in adipose tissue and skeletal muscle. Progesterone stimulates deposition of body fat but had catabolic effects on protein metabolism. Provisional evidence is offered that the steroid may influence ketone body production by the liver as well. When these steroid actions are considered together, their most relevant expression appears to be the physiologic changes observed during normal pregnancy.

Adipose Tissue↗
PubMed1982

Relation of body fat distribution to metabolic complications of obesity.

The importance of body fat distribution as a predictor of metabolic aberrations was evaluated in 9 nonobese and 25 obese, apparently healthy women. Plasma glucose and insulin levels during oral glucose loading were significantly higher in women with predominantly upper body segment obesity than in women with lower body segment obesity. Of the former group, 10 of 16 subjects had diabetic glucose tolerance results, while none of the latter group was diabetic. Fasting plasma triglyceride levels were also significantly higher in the upper body segment obese women. The site of adiposity in the upper body segment obese women was comprised of large fat cells, while in the lower body segment obese subjects, it was formed of normal size cells. In both types of obesity, abdominal fat cell size correlated significantly with postprandial plasma glucose and insulin levels. Thigh fat cell size gave no indication as to the presence of metabolic complications. Thigh adipocytes were also resistant to epinephrine-stimulated lipolysis, presumably due to an increase in alpha-adrenergic receptors. Thus, in women, the sites of fat predominance offer an important prognostic marker for glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. This association may be related to the disparate morphology and metabolic behavior of fat cells associated with different body fat distributions.

Adipose Tissue↗
PubMed1982

Influence of sex and obesity on plasma catecholamine response to isometric exercise.

The effects of obesity and gender on plasma catecholamine levels were studied in 10 lean men, 10 lean women, and 10 obese women. Measurements (mean +/- SE) were obtained sequentially after 30 min of bedrest, 10 min of standing, and 5 min of sustained handgrip, and following 15 min of rest while standing. The supine plasma norepinephrine (NE) levels were comparable among the 3 groups, whereas plasma epinephrine (E) was lowest in obese women (14 +/- 2 pg/ml), intermediate in lean women (19 +/- 2 pg/ml), and highest in lean men (29 +/- 5 pg/ml). Peak plasma levels were reached during handgrip. E values in men (139 +/- 27 pg/ml) exceeded those in lean women (71 +/- 9 pg/ml; P less than 0.05), and both were higher than the E response in obese women (38 +/- 7 pg/ml; P less than 0.01). While peak plasma NE levels in lean women (654 +/- 62 pg/ml) and obese women (524 +/- 46 pg/ml) were comparable, both were significantly lower than the NE response in lean men (1014 +/- 114 pg/ml; P less than 0.02). Increments in plasma FFA during handgrip were 21% and 28% above values during standing (P less than 0.005) in lean men and lean women, respectively, whereas no net increment occurred in obese women. The excursion of plasma beta-hydroxybutyrate in recovery was 59% above the standing concentration for lean women (P less than 0.05), but no net increments were observed in obese women or lean men. We conclude that obesity in women is attended by suppressed plasma E responses to isometric exercise, which may explain subnormal excursions of plasma FFA and beta-hydroxybutyrate during handgrip and recovery, respectively. Lean men have greater plasma elevations of E and NE during isometric exertion than women, suggesting an influence of sex on plasma catecholamine regulation.

3-Hydroxybutyric Acid↗
PubMed1981

Metabolic response to starvation. II. Effects of sex steroid administration to pre- and postmenopausal women.

Premenopausal women become more ketotic than do men during short term starvation. The possible influence of female sex steroids on ketosis during an 84-hr fast was studied in premenopausal women receiving combined oral contraceptive steroids. The results were compared to age and weight-matched women on no steroid birth control regimen. Although concentrations of several plasma substrates, insulin, and glucagon were measured throughout the fast, no differences between groups were observed with the exception of the 36-hr interval. At this time total plasma ketones and betahydroxybutyrate were significantly higher in women receiving oral contraceptives. In a second study six postmenopausal women were investigated in a similar fashion during a 36-hr fast. The procedure was repeated following a 5 day treatment regimen of oral estradiol and medroxyprogesterone acetate. After sex steroid treatment, total plasma ketones and betahydroxybutyrate concentrations exceeded control values significantly at 36 hr while plasma alanine and free fatty acid levels were significantly lower. The results suggest that oral estrogen-progestin combinations increase the ketogenic response of pre- and postmenopausal women during the early phases of total starvation. This hormonal effect may explain, in part, why women are more sensitive to fasting than are men.

Adult↗
PubMed1981

Fluctuations of calcium, phosphorus, sodium, potassium, and chlorine in single alpha and beta cells during glucose perifusion of rat islets.

To study the relationship between islet hormonal secretion and intracellular content of five elements, a rat islet perifusion technique was used in 24 paired experiments. Control and experimental chambers each containing 100 islets, received 2.8 and 16.7 mM D-glucose, respectively. Effluent was collected frequently for hormone measurements. At eight different time intervals form 0--30 min islets were fixed and prepared for scanning electron microscopy. Over 900 unobscured alpha and beta cells were selected by size and shape criteria. Energy dispersive x-ray analysis was applied to each single cell to determine relative content of calcium (Ca), potassium (K), sodium (Na), chlorine (Cl), and phosphorus (P). Experimental chambers exhibited typical acute (0--9 min) and second phase (10--30 min) insulin secretion in association with suppression of glucagon release after 10 min. At 2 min an abrupt upward K spike in both alpha and beta cells was followed at 3--4 min with a 1.5- to 2-fold rise of Ca and a reciprocal decrease in K, Na, Cl, and P. From 3 to 30 min biphasic insulin secretion. Reduced alpha cell calcium after 6 min preceded suppression of glucagon secretion. After 2 min K related inversely to Ca content in both alpha and beta cells. These results could not be reproduced when D-galactose was substituted for D-glucose. We conclude that sequential changes of Ca content that are reciprocally related to K are predictive of beta cell insulin release and suppression of alpha cell glucagon secretion.

Animals↗
PubMed1981

Plasma epinephrine disturbances in diabetic subjects during standing and after isometric exercise.

Effects of isometric exercise on plasma norepinephrine (NE), epinephrine (E), and related factors (mean +/- SE) were studied in 10 healthy, insulin-dependent diabetic subjects and 10 matched control adults. Measurements were obtained after 30 min of bedrest and sequentially during 10 min of upright posture and 5 min of handgrip and after 15 min of rest while still upright. In control and diabetic groups, respectively, basal plasma NE (180 +/- 22 vs. 169 +/- 27 pg/ml) and E (24 +/- 4 vs. 33 +/- 8 pg/ml) as well as heart rate and mean blood pressure did not differ. However, E responses to standing and recovery from isometric exercise in diabetic subjects significantly exceeded control values 2-fold (P less than 0.05) and were accompanied by exaggerated increases in heart rate (P less than 0.05); whereas NE, mean blood pressure, plasma GH, and glucagon profiles during all periods were not significantly different. Exaggerated E responses in diabetic patients were associated with plasma glucose increments above resting values during grip and recovery of 21 and 41 mg/dl, respectively; slightly though significantly higher plasma cortisol responses, and low, fixed concentrations of plasma insulin. These findings contrasted to corresponding glucose increments in control subjects of only 3-4 mg/dl and a 2-fold rise in plasma insulin during recovery. It is concluded that E disturbances in this diabetic group after standing and isometric exercise are physiologically linked to abnormal increments in heart rate and plasma glucose concentrations. These observations suggest that altered E, as opposed to NE, may represent an early defect of the sympathoadrenal system in diabetes mellitus.

Blood Glucose↗
PubMed1980

Correlation of hyperprolactinemia with altered plasma insulin and glucagon: similarity to effects of late human pregnancy.

Plasma glucose and insulin concentrations were measured during oral glucose and iv tolbutamide tolerance tests in nine women with hyperprolactinemia and the amenorrheagalactorrhea syndrome (AGS). Glucose tolerance curves, basal insulin levels, and postchallenge plasma insulin responses were significantly higher in AGS women compared to those in an age- and weight-matched control group. Fasting plasma glucagon concentrations were unaltered in AGS, but suppression of the hormone after oral glucose was greater and more prolonged relative to the control response. Oral glucose tolerance tests were performed on nine normal women during late pregnancy who had physiological hyperprolactinemia comparable to that in the AGS group. Glucose tolerance curves, exaggerated plasma insulin responses, and glucagon suppression resembled those observed in the AGS women. These results suggest that elevated plasma PRL concentrations may contribute to the development of hyperinsulinemia and accentuated glucagon suppression in response to glucose that is characteristic of late human pregnancy.

Adult↗
PubMed1979

Changes in lipoprotein composition during the menstrual cycle.

Composition of major plasma lipoproteins was studied in 14 normal women during different phases of the menstrual cycle for three consecutive months. The results were compared to measurements in ten normal age-matched men for a comparable period, to delineate possible sex differences in lipoprotein metabolism in young adults. Blood samples were obtained every 3--5 days after a 14-hr overnight fast and processed for determinations of total plasma cholesterol, LDL- and HDL-cholesterol, and apoproteins B and A-1. In premenopausal women, a significant, 10%--25% cyclical suppression of total plasma cholesterol, LDL-Chol, and LDL-apoB occurred during the luteal phase, which was significantly lower than unchanging concentrations found in men at any time interval. HDL-Chol remained in a significantly higher fixed concentration range in the female subjects as compared to the men. These sex differences in lipoprotein metabolism may have relevance to the reduced susceptibility of premenopausal women to atherosclerosis.

Adult↗
PubMed1979

Plasma free tryptophan, brain serotonin, and an endocrine profile of the genetically obese hyperglycemic mouse at 4--5 months of age.

Genetically obese hyperglycemic mice (ob/ob) were compared with their nonlittermate lean controls at 4-5 months of age with regard to brain serotonin, pituitary ACTH content, and circulating levels of glucose, glucagon, insulin, TSH, T3, T4, total tryptophan and free tryptophan. Brain serotonin pituitary ACTH content, and plasma insulin, glucose, total tryptophan, and free tryptophan were all significantly higher in obese mice than in the controls. TSH, T3, and T4 were not significantly different in obese mice vs. controls, suggesting that the obese mouse is euthyroid. Fasting improved but failed to normalize the glucose and insulin levels or insulin to glucagon ratios. Since serotonin is an important neurotransmitter with regard to hypothalamic-pituitary function and since its levels in the brain are dependent on the availability of tryptophan, the findings of elevated levels of free tryptophan in the plasma and serotonin in the brain of the obese hyperglycemic mouse may help to explain some of the previously observed abnormalities of pituitary hormone secretion in these animals.

Adrenocorticotropic Hormone↗