The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog

The aim of the present experiments was to determine the role of insulin and glucagon in the regulation of basal glucose production in dogs fasted overnight. A deficiency of either or both pancreatic hormones was achieved by infusin somatostatin (1 mug/kg per min), a potent inhibitor of both insulin and glucagon secretion, alone or in combination with intraportal replacement infusions of either pancreatic hormone. Infusion of somatostatin alone caused the arterial levels of insulin and glucagon to drop rapidly by 72+/-6 and 81+/-8%, respectively. Intraportal infusion of insulin and glucagon at rates of 400 muU/kg per min and 1 ng/kg per min, respectively, resulted in the maintenance of the basal levels of each hormone. Glucose production was measured using tracer (primed constant infusion of [3-3H]glucose) and arteriovenous difference techniques. Isolated glucagon deficiency resulted in a 35+/-5% (P less than 0.05) rapid and sustained decrease in glucose production which was abolished upon restoration of the plasma glucagon level. Isolated insulin deficiency resulted in a 52+/-16% (P less than 0.01) increase in the rate of glucose production which was abolished when the insulin level was restored. Somatostatin had no effect on glucose production when the changes in the pancreatic hormone levels which it normally induces were prevented by simultaneous intraportal infusion of both insulin and glucagon. In conclusion, in the anesthetized dog fasted overnight; (a) basal glucagon is responsible for at least one-third of basal glucose production, (b) basal insulin prevents the increased glucose production which would result from the unrestrained action of glucagon, and (c) somatostatin has no acute effects on glucose turnover other than those it induces through perturbation of pancreatic hormone secretion. This study indicates that the opposing actions of the two pancreatic hormones are important in the regulation of basal glucose production in the postabsorptive state.     

Pantothenic acid, coenzyme A, and human chronic ulcerative and granulomatous colitis

To investigate further an apparent relationship between chronic ulcerative and granulomatous colitis and pantothenic acid deficiency, colonic tissues obtained at the time of colectomy in 29 patients with these disorders were assayed for pantothenic acid and for coenzyme A (CoA) activity. For comparison, normal colonic tissues free of pathological lesions were obtained from 31 patients having colectomy for carcinoma or diverticulitis. Plasma, red blood cells, and colonic mucosa were assayed microbiologically for free and total pantothenic acid. The activity of CoA in colonic mucosa was determined by assaying the acetylation of sulfanilamide. Concentrations of free, bound, and total pantothenic acid in blood and in colonic mucosa did not differ between the two groups of patients. Bound pantothenic acid increased linearly with total pantothenic acid. Colonic mucosa concentrated free pantothenic acid to about 50 times the level of blood, and pantothenic acid in red cells was similar to the concentration in plasma. Compared to normal gut mucosa, CoA activity was markedly low in mucosa from patients with chronic ulcerative or granulomatous disease despite the presence of normal amounts of free and bound pantothenic acid. A block in the conversion of bound pantothenic acid to CoA in diseased mucosa is suggested.     

Effect of galactose and sugar substitutes on blood insulin levels in normal and obese individuals

Eighteen male patients between the ages of 25 and 50 were given on a double blind randomized basis (A) 40 gms. galactose (B) 50 gms. arabinogalactan and 0.11 gm. sodium saccharin (C) 2 gm. methyl cellulose and 0.083 gm. sodium saccharin and (D) 4 gm. galactose, all in 200 ml water. Blood glucose, galactose and insulin levels were determined during a six hour period before and after ingestion. The three first mentioned solutions tasted equally sweet, the fourth was essentially tasteless. None of these feedings altered plasma insulin or glucose levels. It appears that in contrast to other conclusions reached by earlier investigators sweet taste is unable to induce insulin secretion through neurogenic pathways.     

Hemodynamic determinants of the time-course of fall in canine left ventricular pressure

The hemodynamic determinants of the time-course of fall in isovolumic left ventricular pressure were assessed in isolated canine left ventricular preparations. Pressure fall was studied in isovolumic beats or during prolonged isovolumic diastole after ejection. Pressure fall was studied in isovolumic relaxation for isovolumic and ejecting beats (r less than or equal to 0.98) and was therefore characterized by a time constant, T. Higher heart rates shortened T slightly from 52.6 +/- 4.5 ms at 110/min to 48.2 +/- 6.0 ms at 160/min (P less than 0.01, n = 8). Higher ventricular volumes under isovolumic conditions resulted in higher peak left ventricular pressure but no significant change in T. T did shorten from 67.1 +/- 5.0 ms in isovolumic beats to 45.8 +/- 2.9 ms in the ejecting beats (P less than 0.001, n = 14). In the ejecting beats, peak systolic pressure was lower, and end-systolic volume smaller. To differentiate the effects of systolic shortening during ejection from those of lower systolic pressure and smaller end-systolic volume, beats with large end-diastolic volumes were compared to beats with smaller end-diastolic volumes. The beats with smaller end-diastolic volumes exhibited less shortening but similar end-systolic volumes and peak systolic pressure. T again shortened to a greater extent in the beats with greater systolic shortening. Calcium chloride and acetylstrophanthidin resulted in no significant change in T, but norepinephrine, which accelerates active relaxation, resulted in a significant shortening of T (65.6 +/- 13.4 vs. 46.3 +/- 7.0 ms, P less than 0.02). During recovery from ischemia, T increased significantly from 59.3 +/- 9.6 to 76.8 +/- 13.1 ms when compared with the preischemic control beat (P less than 0.05). Thus, the present studies show that the time-course of isovolumic pressure fall subsequent to maximum negative dP/dt is exponential, independent of systolic stress and end-systolic fiber length, and minimally dependent on heart rate. T may be an index of the activity of the active cardiac relaxing system and appears dependent on systolic fiber shortening.     

The thromboembolic risk of the pill

In this review, the clinical reality, the statistical risk, and the frequency of thromboembolism in pill users are evaluated, 6 cases described, and premonitory signs, treatment, and etiology are discussed. Clinically these thromboembolisms appear in unlikely subjects and unusual bodily locations such as the mesenteric veins, without warning. The risks are 8-11 times higher for pulmonary thrombosis, 3-6 times higher for myocardial infarction, based on previously used higher dosed pills. The frequency is about .5-1/1000, or 500-1000/year in France. Some of the cases described used pills with less than .05 mg estrogen, some were heavy smokers, 1 woman died, 1 had a lower extremity amputation, and 1 woman had demonstrated IgG lamda antibodies against ethinyl estradiol. Premonitory signs are rare, and unsually ignored. The immediate action is to stop the pill and start anticoagulants. The cause of these disorders is not known in detail, but is presumed to be estrogens, therefore, low-dose pills, i.e., those with .05 or .03 mg ethinyl estradiol, should be used if possible. Other risk factors are surgery, age, immobilization, history of vein disorders, smoking, hyperlipidemia, hypertension, especially since the pill potentiates hypertension, hyperlipidemia, and hypercoagulation. Some mechanisms proposed are hyperlipidemia, disturbed blood coagulation factors, decreased fibrinolysis, alterations in the blood vessel endothelium and immunity against the estrogen in the pill.     

Study of TRH in the postganglionic sypnasis of the isolated human vas deferens

Cummulative dose-response curves to l-noradrenaline and in presence of different concentrations of TRH (10(-3), 10(-4), 10(-5), 10(-6), 10(-7), and 10(-8) M) were investigated. 25 segments of vas deferens (escrotal tract) were obtained from different surgical patients of urological disorders. At the lower concentration (greater than 10(-7) M), we can not appreciate any influence of TRH on the l-noradrenaline response. Nevertheless there was a reduction of response to l-noradrenaline, with displacement of the curves to the right side, for the high concentrations, and a proportional ratio to the concentration to TRH.     

Computerized tomography in the diagnosis of cerebral atrophy

Computerized tomograms were studied of 67 adults whose lumbar pneumoencephalograms were normal or showed ventricular dilatation with or without widening of the sulci. The maximum ventricular area, measured from 80 x 80 matrix printouts, correlates well with measures of ventricular size on the pneumoencephalogram. An area of 10 cm2 is suggested as the upper limit of normal. The correlation between measures of sulcal width on computerized tomography and pneumoencephalography is less precise, but normal sulci and gross degrees of cortical atrophy can be identified.