Glycogen synthase, synthase phosphatase, and phosphorylase response to glucose in somatostatin-pretreated intact rats.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to F Q Nuttall.
Explore the source record for details and available documents.
Muscle capillary basement membrane width (MCBMW) was measured in 18 myotonic dystrophy patients and compared with that in age- and sex-matched normal and diabetic subjects. The MCBMW in myotonic dystrophy patients (773 +/- 258 A) was significantly thinner than in normal subjects (925 +/- 181 A, P less than 0.05) or in diabetics (1224 +/- 614 A, P less than 0.01). An increase in MCBMW with advancing age was present in all groups but was greatest in the myotonic dystrophy groups (r = +0.59, P less than 0.01). There was no relation between MCBMW and either the degree of glucose intolerance or insulin hypersecretion in the myotonic dystrophy group, though none had fasting hyperglycemia. This is the first report of a condition associated with thinner-than-normal capillary basement membrane.
Segmental pancreatic allotransplants were performed intraperitoneally in pigs with and without ligation of the duct. Exocrine pancreatic function was suppressed by the administration of glucagon. All recipients also received high doses of methylprednisolone for the first 10 days after transplant as well as cyclophosphamide until death or sacrifice. Some animals received antilymphocyte globulin (ALG) in addition. Diabetes was induced by total panreatectomy. Allotransplantation in pancreatectomized animals was successful in preventing hyperglycemia for up to 33 days of observation. ALG in the dosage used did not show any beneficial effects and varying degrees of rejection occurred in the majority of these unmatched animal pairs. Grafts without ligation of the duct seemed to show the best preservation of tissue because of absence of obstructive damage following duct ligation. Of significance is the fact that no intraperitoneal inflammatory or infectious complications occurred in recipients of either duct-ligated or unligated grafts, presumably because of suppression of exocrine function with glucagon and the reabsorptive capability of the peritoneal surface. We speculate that this is a satisfactory physiological model for continued trials in pancreatic transplantation, although antirejection therapy was far from satisfactory.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In normal fed rats, glycogen synthase D phosphatase activity in a glycogen pellet preparation was only partially inhibited (approximately 50%) by high concentrations of EDTA. However, the proportion of phosphatase activity inhibited by EDTA was markedly and rapidly (15 s) increased following glucagon or cAMP administration. Epinephrine administration did not alter the proportion of activity inhibited by EDTA. Glucose administration rapidly (2 min) reduced the proportion of synthase phosphatase activity inhibitable by EDTA. That is, the effect of glucose was just the opposite of that produced by glucagon or cAMP. Insulin administration had no effect on phosphatase activity. Synthase phosphatase activity assayed in the absence of EDTA was similar in all groups except for a moderate increase after glucose administration. Addition of Mg2+ completely reversed EDTA inhibition. Phosphorylase phosphatase activity in each group was not modified by addition of EDTA, although the percentage of phosphorylase in the alpha form was higher in glucagon-treated and lower in the glucose-treated animals as expected. These data suggest the presence of rapidly interconvertible forms of either synthase phosphatase or its substrate synthase D, detectable as a change in EDTA inhibitability and subject to glucose and glucagon control.
Synthase phosphatase, phosphorylase phosphatase and histone phosphatase in rat liver were measured using as substrates purified liver synthase D, phosphorylase alpha and 32P-labelled phosphorylated f1 histone, respectively. The three phosphatase enzymes had different sedimentation characteristics. Both synthase phosphatase and phosphorylase phosphatase were found to sediment with the microsomal fraction under our experimental conditions. Only 10% of histone phosphatase was in this fraction; the majority was in the cytosol. No change in histone phosphatase was observed in the adrenalectomized fasted rat whereas synthase phosphatase and phosphorylase phosphatase activities were decreased 5-10 fold. Fractionation of liver extract with ethanol produced a dissociation of the three phosphatase activities. When a partially purified fraction was put on a DEAE-cellulose column, synthase phosphatase and phosphorylase phosphatase both exhibited broad elution profiles but their activity peaks did not coincide. Histone phosphatase eluted as a single discrete peak. When the supernatant of CaCl2-treated microsomal fraction was put on a Sepharose 4B column, the majority of synthase phosphatase was found to elute with the larger molecular weight proteins whereas the majority of phosphorylase phosphatase eluted with the smaller species. Histone phosphatase migrated as a single peak and was of intermediate size. Synthase phosphorylase phosphatase by synthase D (Ki approximately 2 units/ml). The inhibition of synthase phosphatase by phosphorylase alpha was kinetically non-competitive with substrate. Histone phosphatase activity was not inhibited by synthase D or by phosphorylase alpha. The above results suggest that different proteins are involved in the dephosphorylation of synthase D, phosphorylase alpha and histone in the cell.
Motor nerve conduction velocity (MNCV) was measured in three peripheral nerves in each of 24 patients with myotonic dystrophy having various degress of associated glucose intolerance and was compared with results in a control group. Both groups had similar glucose tolerance and were matched for age and adiposity. The mean MNCV in the ulnar, median, and peroneal nerves in the myotonic dystrophy group were all significantly slowed (P less than .01). This peripheral nerve dysfunction, usually subclinical, is yet another manifestation of this multisystem disease and is unrelated to the associated glucose intolerance.
The prevalence of diabetes in Minnesota school-age children was found to be one per 529 students (1.89 per 1,000), 95 per cent of whom were receiving insulin. Data were obtained by a mail survey of the public schools in the state. Enrollment in public schools represents 90 per cent of the student population in Minnesota, and data were received from 96 per cent of the public schools. This return rate by schools accounts for 95 per cent of the total student enrollment. Diabetes increased linearly with age, representing a yearly prevalence increase of 0.16 cases per 1,000 students.
The administration of commercial phosphate cathartic in conventional doses to normal subjects prior to barium enema resulted in a striking increase in serum phosphorus levels followed by a decline in serum calcium levels in all subjects. Changes were highly significant (P less than .01) when compared with control subjects who were prepared for the same procedure with magnesium citrate. Levels of serum potassium also decreased significantly (P less than .01) but not serum sodium, chloride, bicarbonate, or magnesium.
Explore the source record for details and available documents.
Using substrates purified from liver, the apparent Km values of synthase phosphatase ([UDPglucose--glycogen glucosyltransferase-D]phosphohydrolase, EC 3.1.3.42) and phosphorylase phosphatase (phosphorylase a phosphohydrolase, EC 3.1.3.17) were found to be 0.7 and 60 units/ml respectively. The maximal velocity of phosphorylase phosphatase was more than a 100 times that of synthase phosphatase. In adrenalectomized, fasted animals there was a complete loss of synthase phosphatase but only a slight decrease in phosphorylase phosphatase when activity was measured using endogenous substrates in a concentrated liver extract. When assayed under optimal conditions with purified substrates, both activities were present but had decreased to very low levels. Mixing experiments indicated that synthase D present in the extract of adrenalectomized fasted animals was altered such that it was no longer a substrate for synthase phosphatase from normal rats. Phosphorylase a substrate on the other hand was unaltered and readily converted. When glucose was given in vivo, no change in percent of synthase in the I form was seen in adrenalectomized rats but the percent of phosphorylase in the a form was reduced. Precipitation of protein from an extract of normal fed rats with ethanol produced a large activation of phosphorylase phosphatase activity with no corresponding increase in synthase phosphatase activity. Despite the low phosphorylase phosphatase present in extracts of adrenalectomized fasted animals, ethanol precipitation increased activity to the same high level as obtained in the normal fed rats. Synthase phosphatase and phosphorylase phosphatase activities were also decreased in normal fasted, diabetic fed and fasted, and adrenalectomized fed rats. Both enzymes recovered in the same manner temporally after oral glucose administration to adrenalectomized, fasted rats. These results suggest an integrated regulatory mechanism for the two phosphatase.
Postprandial plasma glucose, insulin and triglyceride responses were determined in 12 normal subjects (7 male and 5 female) fed a standard diet composed of typical American foods; the three meals were identical for each subject. A significant postprandial rise in glucose and insulin was observed. They were closely related temporally in the early postabsorptive period. However, in the late post-absorptive phase insulin decline was generally slower than the glucose decline. A considerable difference in the glucose and insulin response was observed between males and females. Fasting plasma glucose and insulin concentrations were lower in the women. Following each meal the peak plasma glucose was lower in the women, but the difference was significant only following breakfast (p less than 0.02). The area under the glucose curve following breakfast was also lower (p less than 0.01) in the women. In the men the maximal postprandial glucose concentration and the postprandial glucose area remained stable throughout the day, but there was an increase in peak insulin concentration and insulin area after dinner. In contrast, in the women the maximal postprandial glucose concentration and the postprandial glucose area increased throughout the day, but the peak insulin concentration and insulin area did not change. Plasma trigylcerides increased with breakfast and remained elevated throughout the day. Both fasting and postprandial mean triglycerides were higher in the men, but this did not reach statistical significance. The circulating pancreatic glucagon concentration, determined in 4 subjects, was unaffected by meals and remained stable throughout the day.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The literature now contains reports of many cases of aldosterone deficiency. Usually, the presenting features are persistent hyperkalemia and tendencies to serious urinary sodium loss and hypotension. A classification of defects leading to pathologic hypofunction of the renin-angiotensin-aldosterone system (RAAS hypofunction) is presented, with emphasis on idiopathic hyporeninemia (probably the most common). Criteria for diagnosis are (1) normal adrenal glucocorticoid function, (2) low aldosterone excretion under basal and stimulated conditions, and (3) renal tubular responsiveness to exogenous mineralocorticoid. The condition is effectively managed with mineralocorticoid replacement therapy and should be considered in the presence of unexplained persistent hyperkalemia, hyponatremia, or postural hypotension.
Explore the source record for details and available documents.
We describe a patient with histiocytosis X and compulsive water drinking. The association of diabetes insipidus with histiocytosis X is well recognized, and this patient was initially considered to have diabetes insipidus. It was only after further testing that the proper diagnosis was made.