Capillary permeability in healthy males with different insulin response to glucose

The capillary permeability in human skeletal muscle, expressed as capillary diffusion capacity (CDC) for 51Cr-EDTA, was determined during exercise with a local clearance method in two groups of healthy male subjects: a younger group with a mean age of 30 years and an older one with a mean age of 58 years. The main finding was that, in both age groups, CDC was significantly negatively correlated to the early phase of insulin response to an intravenous glucose load. No correlation was found between CDC and peripheral insulin sensitivity. CDC was significantly higher in the older age group (P less than 0.01) independent of insulin response, blood flow and body weight. These data indicate that subjects with low insulin response to glucose have a higher capillary permeability than high responders, and that muscle capillary permeability increases with age.     

The Role of Glucagon,Catecholamines and Cortisol in Counterregulation of Insulin-induced Hypoglycemia in Normal Man

ABSTRACT To study the response of glucose counterregulation to insulin-induced hypoglycemia, six normals were given a 4-hour infusion of insulin (2.4 U/h) ± somatostatin (50 μg/h). Supplementary glucagon (1.5 or 3.0 ng/kg/min) was given in additional experiments. In a separate study, glucagon was supplemented for 4 hours as a constant rate infusion (3.25 ng/kg/min) or at rates stepwise increasing from 1.5 to 5.0 ng/kg/min. Insulin decreased blood glucose by 1.5 mmol/1 and simultaneous suppression of glucagon resulted in a more pronounced hypoglycemia enhancing the adrenaline and Cortisol responses. The hyperglycemic effect of glucagon substitution (3 ng/kg/min) faded out after about 2 hours, whereafter exaggerated adrenaline and Cortisol responses to hypoglycemia were seen. A comparison between the effects of steady state hyperglucagonemia and gradually appearing hyperglucagonemia on the counterregulation of hypoglycemia revealed no significant differencies in glucose, adrenaline and Cortisol responses to insulin. It is concluded that the glycemic effect of glucagon is transient in the hypoglycemic state. When the hepatic responsiveness to this hormone is decreased during hypoglycemia, adrenaline becomes the essential protective factor.     

Genetic and Environmental Determinants for Lipoprotein Concentrations in Blood

ABSTRACT Path and segregation analyses have been performed on cholesterol and triglyceride contents of serum as well as on very low, low and high density lipoproteins in 78 Swedish nuclear families. The effect of environmental variables like alcohol and smoking on the concentrations of the different lipoproteins has been studied. Genetic heritability was 0.16-0.68 for the cholesterol fractions and 0-0.56 for the triglyceride fractions. No major gene was evident for any of the variables studied.     

Release of gastrin from the skeletal muscles and from the antral mucosa in cats induced by sulfonuric drugs

The present observations indicate that sulfonuric drugs release gastrin both from peripheral nerves in striated muscles and from endocrine-like cells in the gastrointestinal tract. Gastrin appears in perfusates of extirpated cat legs after administration of tolbutamide or glibenclamide (5–50 μg/kg or 5–500 μg/kg perfused tissue respectively) to the perfusion medium. Furthermore gastrin is released into the portal vein of cats after i.v. administration of glibenclamide (5–50 μg/kg). The finding that sulfonuric drugs not only release insulin from β-cells in the pancreas, but also gastrin from gastrin producing cells in the stomach as well as from nerve fibers in the skeletal muscles, indicate that sulfonuric drugs have more wide spread effects than previously assumed. Possible consequences of the drug induced release of peptides from peripheral nerves as well as of the release of gastrin from the gastrointestinal tract are discussed.     

Using post-mortem interviews at the community level: an example from Yemen

Premature death is a tragedy especially when it is preventable.Information on the main causes of death in a community can stimulatethat community into action to change the situation. This paper describes a study conducted with and for a ruralcommunity in the highlands of the Republic of Yemen. Researcherscollected information on the cause of death of the childrenof each ever-married woman, as part of a birth history interview.Researchers then presented the results to the community throughreports and seminars. Many of the main causes of death - diarrhoea,respiratory infections, birth trauma and accidents - were surprisinglycommonplace. The community then organized a programme to preventthe major problems.     

Impaired Counter Regulation of Hypoglycemia in a Group of Insulin-dependent Diabetics with Recurrent Episodes of Severe Hypoglycemia

Abstract The counterregulatory response to insulin-induced hypoglycemia was investigated in 22 insulin-dependent diabetics (IDD) with recurrent hypoglycemia and in 6 healthy volunteers. Hypoglycemia was induced by a constant rate infusion of insulin (2.4 U/h) up to four hours. Conventional insulin therapy was changed to an i.v. infusion of regular insulin 24 hours prior to the experiment. The presence of diabetic autonomic neuropathy was evaluated by respiratory sinus arrhythmia and Valsalva maneuver. In healthy subjects, blood glucose was decreased to 2.5 mmol, here reaching steady state level and giving rise to marked glucagon and growth hormone (GH) responses. The majority of IDD (group A) reached a slightly lower steady state glucose level and exhibited similar glucagon and GH responses while the epinephrine response was augmented. Six IDD (group B) showed a continuous decrease in blood glucose to 1.2+0.1 mmol/l at which level the infusion of insulin was discontinued due to neuroglucopenic symptoms. These subjects had no glucagon and epinephrine responses while their GH and cortisol responses were normal. A comparison of the diabetic groups revealed a longer duration of diabetes and a more impaired autonomic nervous function in group B while glycosylated hemoglobin was similar. It is concluded that most IDD have normal hormonal responses (epinephrine, glucagon, GH, cortisol) and normal counterregulartory capacity to hypoglycemia induced by a prolonged infusion of a moderate dose of insulin. Some patients with long-term diabetes and impaired capacity to counteract hypoglycemia exhibit deficient glucagon and epinephrine responses to hypoglycemia.     

Stimulation by calcium and barium of somatostatin release. Evidence for lower sensitivity of D- vis-à-vis B- and A-cells

To address the question whether a “second messenger” function of calcium differs between D-cells and other cells of the endocrine pancreas, we compared effects of calcium and barium (a calcium substitute) on somatostatin secretion to effects on insulin and glucagon secretion from the perfused pancreas of the rat. 6.5 mmol/l of calcium, when administered early during perfusion, failed to stimulate somatostatin release. 0.05 mmol/l of barium, when added to calcium-deprived media failed to affect somatostatin secretion while 0.5 induced a slight and 2.0 mmol/l a marked and sustained response. Barium-induced insulin release was left-shifted in relation to the somatostatin response, since 0.05 mmol/l of barium stimulated and 0.5 mmol/l evoked a near-maximal insulin response. All concentrations of barium evoked diphasic glucagon responses, i. e. a small (1 min) stimulation followed by sustained inhibition. Addition of 0.5 mmol/l of EGTA to calcium-deprived media abolished D- as well as B- and A-cell secretion. Reintroduction of 0.5–6.5 mmol/l of calcium stimulated somatostatin release; the secretory response was proportionate to the calcium concentration. In contrast, addition of calcium stimulated insulin and glucagon secretion maximally already at 0.5 mmol/l of calcium. We conclude that the D-cell is less sensitive than B- and A-cells to a regulatory effect on secretion exerted by extracellular calcium or barium.