Effects of pregnancy on insulin and glucagon secretion by perifused rat pancreatic islets.
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Biomedical subjects
Publications and source records attributed to R K Kalkhoff.
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After a nine-day control period, six hospitalized obese women were placed on 500 calorie diets and were given 125 IU of human chorionic gonadotropin (HCG) intramuscularly daily for 30 days. Another five obese women received injections of diluent only and consumed identical diets for the same period. Mean weight loss in the HCG-treated group was nearly identical to that achieved by women given the placebo. Reduction of triceps skinfold thickness or circumferential body measurements of the chest, waist, hips, and thighs were not different. Patters of change of a variety of plasma and urine substrates, electrolytes, and hormones were similar in the two groups and consistent with semistarvation and weight loss. These results indicate that HCG has no effects on chemical and hormonal parameters measured and offers no advantage over calorie restriction in promoting weight loss.
The multiple lentigines syndrome is reviewed and a new case is presented. The major features of this syndrome are lentigines and other cutaneous abnormalities, cardiac defects, meurologic defects, cephalofacila dysmorphism, shortness of stature, skeletal anomalies, genitourinary abnormalities, and a family history consistent with an autosomal dominant mode of inheritance. The multiple lentigines syndrome manifests markedly variable expressivity; no single finding is pathognomonic and few patients have all major features. We propose specific criteria for diagnosis.
Plasma glucose, insulin, and alpha-cell glucagon profiles were examined in ten adults with uncomplicated primary hyperparathyroidism before and 8-12 week after surgical removal of a single parathyroid adenoma. Treatment restored abnormal serum calcium and phosphorus concentrations to a normal range and reduced serum parathyroid hormone levels from 47 +/- 4 to 16 +/- 4 mu 1 Eq/ml (normal = 0-40). Plasma glucose curves during 100-g oral glucose tolerance, 30 min intravenous glucose (1.5 g/min), or arginine infusions (1.0 g/min) did not differ before and after surgery. However, basal and peak insulin concentrations were higher before treatment during these tests (p less than 0.05). Basal glucagon levels were unaffected by hyperparathyroidism (72 +/- 7 versus 77 +/- 7 pg/ml). Peak 30 min values after arginine provocation were also similar before and after treatment as was maximal suppression of basal glucagon during glucose infusions. Four patients also received 400 g lean beef meals. Glucose and glucagon responses over 240-min periods were nearly identical before and after surgery despite higher insulin levels before treatment. It is concluded that elevated serum parathyroid hormone and plasma insulin concentrations in primary hyperparathyroidism do not relate to abnormalities of plasma alpha-cell glucagon in the basal state or after glucose, arginine, or protein administration.
To define the relationship between hyperparathyroidism (HPT) and gastric function, 31 patients with HPT were prospectively studied before and 2 to 25 months after parathyroidectomy. The gastrin response to a standard test meal (STM), the basal acid output (BAO), and the peak acid output (PAO) were determined. Parathormone and calcium were elevated in all patients and returned to normal following parathyroidectomy. The mean fasting gastrin concentration, mean integrated gastrin response (IGR) to feeding, mean basal acid output (BAO), and mean peak acid output (PAO) were not changed by successful parathyroidectomy. There was no significant correlation between gastrin concentration or gastrin response to feeding and gastric acid secretion. Eight of 31 HPT patients had fasting gastrin concentrations above normal preoperatively and remained so postoperatively. Hypergastrinemia in six of these eight patients could be explained by the Zollinger-Ellison (Z-E) syndrome or chronic atrophic gastritis. The hypothesis that peptic ulcer disease seen in some HPT patients is the result of calcium-induced hypergastrinemia causing gastric hypersecretion is not supported by this study.
The effect of exogenous glucagon and secretin on resting lower esophageal sphincter (LES) tone during endogenous hypergastrinemia was studied in 2 patients with proven Zollinger-Ellison Syndrome (ZES). Intravenous glucagon and in one patient secretin, in dosages which decrease LES pressure in normals during LES stimulation by exogenous gastrin, caused a decrease in resting LES pressure in the ZES patients. This drop in LES tone occurred both during concomitant serum gastrin rise caused by secretin and serum gastrin decline caused by glucagon. This finding suggests that the action of secretin on LES pressure may be independent on endogenous gastrin, while the glucagon effect on LES tone may be mediated through gastrin.
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Triglyceride metabolism was investigated in groups of fed and fasted rats after 21 days of parenteral estradiol (5 mug daily), progesterone (5 mg daily), or the two steroids in combination. Results were compared with control groups receiving an oil solvent alone. In rats given estradiol separately or combined with progesterone, hypertriglyceridemia was uniformly associated with increased plasma triglyceride entry, estimated with the i.v. Triton WR1339 technique. Progesterone alone had no effect on these parameters. Plasma postheparin lipolytic activity (PHLA), adipose, mammary gland, and protamine-resistant liporotein lipases (LPL) were significantly increased in progesterone-treated rats and significantly decreased in rats receiving estradiol with the exception of mammary gland LPL, which was also increased to a slight extent. The combined regimen reduced plasma PHLA and increased protamine-resistant adipose, and mammary gland LPL activity. Sex steroid treatments had minimal effects on plasma glucose and free fatty acid concentrations, but all increased plasma insulin significantly. Hyperinsulinemia did not parallel changes in body weight or other measured parameters. Linear regression analyses revealed that plasma triglyceride concentrations in all fed, treated rats correlated significantly with triglyceride entry but not very uniformly with plasma or tissue LPL activity. We conclude that estradiol, unlike progesterone, has substantial lipemic effects in the rat which relate best to triglyceride entry. Hyperinsulinemia, changes in body weight, plasma PHLA, and tissue LPL activities did not consistently predict the influence of sex steroid treatment on plasma triglyceride concentrations.
This study evaluates the effect of exogenous glucagon on esophageal motor function in man. Manometric studies were performed using an infused catheter system. Resting lower esophageal sphincter (LES) pressure was monitored before and after intravenous pulse doses of glucagon (1 to 100 mug). The effect of glucagon (0 mug ) on esophageal peristalsis was also studied. Multiple blood samples were taken for determination of glucagon, insulin, and glucose concentration. Glucagon effect on LES pressure was also evaluated after LES stimulation by continuous intravenous infusion and pentagastrin (0.04 mug per kg per min). Glucagon caused a transient significant decrease of LES pressure only at pulse doses (20 and 100 mug) which caused nonphysiological elevation of plasma glucagon levels. The temporal profile of decreased LES pressure correlated closely with maximal blood glucagon levels. Glucagon caused no demonstrable change in esophageal peristalsis. During LES stimulation by pentagastrin, glucagon caused significant transient decreases of LES pressure at doses as low as 1 mug per kg. We conclude that glucagon at sufficient dosage has an inhibitory effect on LES pressure. This inhibitory effect is not mediated through changes in serum insulin or glucose and appears to be pharmacological.
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