The effect of fasting on liver receptors for prolactin and growth hormone

The effects of 3 day fasting on liver prolactin and growth hormone receptors have been investigated in male and female rats. Fasting caused a significant fall in serum immunoreactive insulin (67% decrease), while receptor-reactive somatomedin fell by 82% when measured in whole serum and by 72% when measured in serum fractions following gel chromatography at low pH. Tracer ovine prolactin binding to liver microsomal membranes was reduced by 55% on fasting in females, but unchanged in males. Tracer bovine growth hormone binding fell significantly in both sexes. Analysis of competitive binding curves showed the decreased binding to be due to a loss of prolactin receptors in females, and of high affinity (but not low affinity) growth hormone receptors in males and females. Significant correlations were seen between serum insulin and tracer prolactin (females) and growth hormone (males and females) binding to liver membranes. Correlations between serum insulin and liver high affinity growth hormone binding sites were particulary significant (r = 0.899 in females, r = 0.910 in males). It is proposed that the hypoinsulinemia of fasting causes a loss of high affinity growth hormone receptors in the liver, which could result in a relative hepatic resistance to growth hormone and a decreased hepatic generation of somatomedin.     

Ultrastructural responses by Golgi apparatus of rat submandibular gland to beta-adrenergic, alpha-adrenergic, and cholinergic stimulation

Rat submandibular gland tissue pieces were stimulated in vitro for 30 min with a beta-adrenergic agent or a cyclic AMP analog to stimulate protein secretion, or with alpha-adrenergic or cholinergic agents or a Ca2+ ionophore to stimulate fluid secretion. Acinar cells were examined by transmission electron microscopy. In control tissue, acinar cells showed little evidence of secretory activity. The Golgi apparatus was sparse and was associated with a few small, immature secretory granules with fine fibrillar contents. Following secretory granule discharge stimulated by isoproterenol or dibutyryl cyclic AMP, acinar cells were constricted, and had extensive basolateral membrane folding and tightly packed rough endoplasmic reticulum. Golgi complexes were prominent and had multiple small granules with filamentous contents. After stimulation of fluid secretion by alpha-adrenergic agents (epinephrine, phenylephrine), or cholinergic agents (acetylcholine, carbachol, pilocarpine), or a Ca2+ ionophore (A23187), the Golgi apparatus had compact concave cisternae enclosing aggregates of tubulovesicles. Acinar cells were distended, basolateral membranes were expanded, and rough endoplasmic reticulum was dilated and vesiculated.     

Maternal vs paternal diabetes: The parental history is different in younger onset versus older onset type 2 diabetes

BackgroundA number of previous studies exploring family history of type 2 diabetes have reported a predominance of maternal diabetes. These studies have not explicitly compared parental history of diabetes across the spectrum of disease onset from youth to later adulthood.MethodsFamily history data from 11,467 patients with type 2 diabetes were extracted from the RPA Diabetes Centre database. Parental histories of diabetes were compared across a range of age of diagnosis strata (15-<30, 30-<40, 40-<50, 50-<60 and 60-<70 years). For the young-onset group (diagnosed between 15 and 30 years of age), associations between parental history of diabetes and the presence of cardio-metabolic risk factors and diabetic complications were also explored.ResultsFor the total cohort and within each age of diagnosis strata, more individuals reported maternal history than paternal history of diabetes. The young-onset group demonstrated the highest prevalence of any parental history of diabetes (60.7%), the highest combined maternal and paternal history (15.8%) and the smallest differential between maternal (25.1%) and paternal (19.7%) history of diabetes. Within the young-onset group, no significant association between parental history and cardio-metabolic risk factors or diabetic complications were identified after a median of 15.0 years of diabetes exposure.ConclusionOverall, our results demonstrate a consistent maternal excess of diabetes which could be consistent with an underlying epigenetic effect. However, the differential between maternal and paternal history is significantly lower in the young-onset group. Earlier emergence of type 2 diabetes may therefore reflect a different interaction and impact of genetic and environmental factors.     

Ultrastructural responses of rat exocrine pancreas to cholecystokinin octapeptide and secretin

The study examines the ultrastructural changes in the rat pancreas stimulated in vivo to secrete zymogen and fluid by the hormones cholecystokinin and secretin, administered either separately or in combination. The octapeptide of cholecystokinin (CCK-OP) (2.5 X 10(-7) g/kg) 5 min after injection produced discharge of electron-dense zymogen into the acinar lumen and intercellular canaliculi (ICC), leaving misshapen, collapsed zymogen granule profiles around the lumen. Five minutes after secretin (7.5 clinical units/kg), acinar cells were distended, rough endoplasmic reticulum was dilated, acinar lumina and ICC were expanded and filled by electron-lucent and flocculent contents, and there were "halo" zymogen granules and pale "vacuoles." Electron-lucent zones surrounding acinar and duct cell microvilli indicated transcellular fluid secretion. When secretin was administered with CCK-OP, the picture was a composite between zymogen and fluid secretory patterns. Zymogen granules took up fluid producing a halo appearance, pale vacuoles formed in acinar cells, and acinar lumina and discharging zymogen granules were of intermediate electron density. The results demonstrated that, although fluid is secreted by duct cells in response to secretin, a major site of secretin-stimulated fluid secretion is acinar cells. Fluid is transported across both cell types by transcellular routes, and the acinar cell fluid secretion is integrated with zymogen discharge. CCK-OP produces partial discharge of undiluted zymogen by exocytosis.     

Stimulation of protein synthesis in isolated hepatocytes by somatomedin

Insulin (1 mU/ml) stimulated the incorporation of 14C-leucine into trichloroacetic acid-precipitable material by isolated hepatocytes from normal and hypophysectomized adult rats and 12-day-old rabbits. Somatomedin (200 ng/ml) purified from human plasma had an insulinlike effect in hepatocytes from hypophysectomized rats and baby rabbits but not from normal rats. This study suggests that, as well as being a site of somatomedin synthesis, the liver may be a target organ for this hormone.     

Localization of coronary artery disease with exercise electrocardiography: correlation with thallium-201 myocardial perfusion scanning

In 61 patients with single vessel coronary artery disease (70 percent or greater obstruction of luminal diameter in only one vessel) and no previous myocardial infarction, the sites of ischemic changes on 12 lead exercise electrocardiography and on thallium-201 myocardial perfusion scanning were related to the obstructed coronary artery. The site of exercise-induced S-T segment depression did not identify which coronary artery was obstructed. In the 37 patients with left anterior descending coronary artery disease S-T depression was most often seen in the inferior leads and leads V₄ to V₆, and in the 18 patients with right coronary artery disease and in the 6 patients with left circumflex artery disease S-T depression was most often seen in leads V₅ and V₆. Although S-T segment elevation was uncommon in most leads, it occurred in lead V₁ or aVL, or both, in 51 percent of the patients with left anterior descending coronary artery disease. A reversible anterior defect on exercise thallium scanning correlated with left anterior descending coronary artery disease (probability [p] < 0.0001) and a reversible inferior thallium defect correlated with right coronary or left circumflex artery disease (p < 0.0001).In patients with single vessel disease, the site of S-T segment depression does not identify the obstructed coronary artery; S-T segment elevation in lead V₁ or aVL, or both, identifies left anterior descending coronary artery disease; and the site of reversible perfusion defect on thallium scanning identifies the site of myocardial ischemia and the obstructed coronary artery.