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Biomedical subjects

C Cochrane

Publications and source records attributed to C Cochrane.

At least 19 recordsLinked to original sources
PubMed1991

Control of expression of insulin resistance and hyperglycemia by different genetic factors in diabetic C57BL/6J mice.

The inheritance of the tendency to develop diet-induced non-insulin-dependent (type II) diabetes was analyzed in crosses between diabetes-prone C57BL/6J (BL/6) mice and diabetes-resistant A/J mice. The effects of a diabetogenic diet on blood glucose and insulin levels, insulin sensitivity, and weight were evaluated in F1 and both (BL/6 X A/J) F1 X BL/6 and (BL/6 X A/J) F1 X A/J backcross mice. These results suggest that diet-induced hyperglycemia is largely determined by a recessive gene and diet-induced insulin resistance by a dominant gene. Analyses of both backcrosses indicated that insulin sensitivity and blood glucose levels were unrelated, suggesting that they are controlled by different genetic factors. This conclusion was supported by data from nine recombinant inbred BXA strains in which no correlation was observed between these variables. Furthermore, insulin sensitivity and body weight correlated differently in the two backcross groups, suggesting that insulin resistance is not simply a function of obesity. The number of genes that predominantly influence diabetic traits was estimated by comparing the variance observed in (BL/6 X A/J) F1 X BL/6 backcross mice with that observed in parental mice. The data suggest that relatively few genes predominantly affect the diabetic phenotype in this murine model.

Animals↗
PubMed1989

Differential glycemic effects of morphine in diabetic and normal mice.

C57BL/6J ob/ob mice, C57BL/6J+/? lean mice and A/J mice were given injections of 10 mg/kg of morphine or an equal volume of saline, and then blood was sampled by retroorbital sinus puncture. In addition, animals from each strain were exposed to a brief experimental stress ten minutes after the administration of morphine or saline. While morphine produced significant increases in serum glucose in albino mice, morphine lowered blood insulin in both C57BL/6J ob/ob and C57BL/6J+/? mice. Morphine significantly lowered blood insulin in A/J mice, but effects in C57BL/6J mice were not significant. In contrast, morphine attenuated blood glucose and insulin during stress in C57BL/6J ob/ob but did not significantly affect either glucose or insulin during stress in lean C57BL/6J or A/J mice. These results are interpreted in the light of other data suggesting that endogenous opiates modulate the effects of sympathetic nervous system activity in type II diabetes.

Animals↗
PubMed1989

Muscarinic stimulation and antagonism and glucoregulation in nondiabetic and obese hyperglycemic mice.

Plasma glucose and insulin responses to a muscarinic agonist (bethanechol chloride) and a muscarinic antagonist (atropine) were evaluated in obese C57BL/6J ob/ob mice and in lean C57BL/6J + /? mice. In lean +/? mice, plasma glucose decreased in response to 1 and 2 micrograms/g bethanechol chloride, whereas insulin increased significantly. In ob/ob mice, insulin increased remarkably in response to bethanechol administration (saline, 632 +/- 80 microU/ml; 2 micrograms/g bethanechol chloride, 1794 +/- 97 microU/ml; n = 10), but surprisingly, plasma glucose also rose significantly (saline, 230 +/- 14 mg/dl; 2 micrograms/g bethanechol chloride, 363 +/- 18 mg/dl, n = 10). This exaggerated hyperglycemia in ob/ob mice was not associated with significant changes in plasma glucagon. Furthermore, administration of propranolol hydrochloride did not diminish bethanechol chloride-induced hyperglycemia in ob/ob mice. Administration of atropine (2.5, 5, and 10 mg/kg body wt) induced a significant decrease in plasma insulin without changes in plasma glucose in ob/ob mice, whereas neither plasma insulin nor plasma glucose changed in lean mice. Finally, conversion of [14C]alanine to glucose was increased in ob/ob mice after bethanechol chloride administration, indicating that muscarinic stimulation increases gluconeogenesis in an animal model of type II (non-insulin-dependent) diabetes.

Animals↗
PubMed1988

Diet-induced type II diabetes in C57BL/6J mice.

We investigated the effects of diet-induced obesity on glucose metabolism in two strains of mice, C57BL/6J and A/J. Twenty animals from each strain received ad libitum exposure to a high-fat high-simple-carbohydrate diet or standard Purina Rodent Chow for 6 mo. Exposure to the high-fat, high-simple-carbohydrate, low-fiber diet produced obesity in both A/J and C57BL/6J mice. Whereas obesity was associated with only moderate glucose intolerance and insulin resistance in A/J mice, obese C57BL/6J mice showed clear-cut diabetes with fasting blood glucose levels of greater than 240 mg/dl and blood insulin levels of greater than 150 microU/ml. C57BL/6J mice showed larger glycemic responses to stress and epinephrine in the lean state than AJ mice, and these responses were exaggerated by obesity. These data suggest that the C57BL/6J mouse carries a genetic predisposition to develop non-insulin-dependent (type II) diabetes. Furthermore, altered glycemic response to adrenergic stimulation may be a biologic marker for this genetic predisposition to develop type II diabetes.

Animals↗
PubMed1987

Exaggerated peripheral responses to catecholamines contributes to stress-induced hyperglycemia in the ob/ob mouse.

The present study investigated the contribution of altered sympathetic reactivity to the stress-induced hyperglycemia observed in the c57BL/6J (ob/ob) mouse, an animal model of type II diabetes. Blood glucose and insulin responses to sympathetic agonist and antagonist administration were evaluated in ob/ob mice and their nondiabetic, lean (ob/?) littermates. In addition, the ability of nutritional status to modify these responses was determined. These studies demonstrated that epinephrine administration to ob/ob mice caused an exaggerated increase in blood glucose and decrease in plasma insulin in ob/ob mice relative to lean littermates. The dose response curve for epinephrine-induced increases in blood glucose were shifted to the left, and the duration of the blood glucose and plasma insulin responses was longer. Differences between ob/ob mice and their nondiabetic littermates were greater when animals were tested in the fasted state. In addition, administration of the alpha adrenergic antagonist phentolamine caused a larger increase in plasma insulin in ob/ob mice than was observed in lean littermates. These results suggest that altered peripheral responses to sympathetic stimuli contribute to stress-induced hyperglycemia in ob/ob mice, and raise the possibility that altered sympathetic function is an etiologic factor in development of diabetes in these animals.

Adrenergic Fibers↗
PubMed1984

Hypoxanthine and oxygen induced lung injury: a possible basic mechanism of tissue damage?

Lung injury was induced in young rats by a continuous infusion of hypoxanthine intravenously and breathing 100% oxygen for 48 h (group 1). Control animals were rats infused glucose and breathing 100% oxygen (group 2), rats infused hypoxanthine in room air (group 3), and untreated rats (group 4). In group 1 rats interstitial and alveolar edema was found with a tendency toward marked margination of polymorphonuclear neutrophils in small vessels (P less than 0.025 compared with group 2). The main elastase inhibitor alpha 1-antitrypsin (alpha-1-PI) was significantly elevated in group 1; 2-, 3- and 5-fold, respectively, when compared with groups 2, 3, and 4. The surfactant phospholipids from alveolar lavage were normal in all groups. The protein-rich fraction of the lavage fluid from group 1 rats inactivated, however, the surface properties of lung surfactant. Minimum surface tension in group 1 rats was 14.5 dyn/cm compared with 7.0 dyn/cm in group 2, 2.9 dyn/cm in group 3 and 3.5 dyn/cm in group 4 (P less than 0.05, group 1 and 2 versus 4). We conclude that the combination of hypoxanthine and high levels of oxygen causes lung injury, possibly via free oxygen radicals. We discuss the possibility that these findings demonstrate a basic pathogenetic mechanism for the hypoxic-hyperoxic insult and can contribute to the understanding of pathogenesis of a variety of diseases both in pediatrics and adult medicine.

Animals↗
PubMed1983

Kinetic analysis of D-xylose absorption in normal subjects and in patients with chronic renal failure.

D-Xylose kinetics were studied in 12 normal subjects and in nine patients with chronic renal failure requiring dialysis (five hemodialysis and four peritoneal dialysis). None of the study subjects had demonstrable gastrointestinal disease. Doses of D-xylose were given intravenously (10 gm) and orally (25 gm) on different nondialysis days in order to determine the distribution and elimination kinetics and the absolute bioavailability of this compound. Our findings were as follows. (1) The nonrenal clearance of D-xylose is markedly reduced in chronic renal failure patients (43.3 vs. 90.9 ml/min, p less than 0.002). (2) D-Xylose is less completely absorbed in patients with chronic renal failure than in normal subjects (48.6% vs. 69.4%, p less than 0.01). (3) The absorption rate of D-xylose is slower in these patients than in normal subjects (0.555 hr-1 vs. 1.03 hr-1, p less than 0.05). (4) The absorption rate is positively correlated with the extent of D-xylose absorption (r = 0.49, p = 0.03). (5) Although peak D-xylose concentrations measured 1 hr after oral administration are well correlated with the extent of D-xylose absorption in normal subjects and in functionally anephric patients (r = 0.59, p less than 0.01), formal kinetic study is required to determine D-xylose bioavailability precisely because of the large variability in peak serum D-xylose concentrations and in the time required to reach these peak concentrations.

Adult↗
PubMed1979

Griseofulvin-induced cholestasis in Swiss albino mice.

Griseofulvin was fed to male Swiss albino mice, which were sacrificed at varying times after the initiation of the feeding. The following were compared with mice fed a control diet: hepatic histology, hepatic weight, plasma glycocholate, glycolithocholate, cholesterol, bilirubin, and alkaline phosphatase. Concurrent with the development of hepatic protoporphyria, a progressive cholestatic lesion was produced with marked bile canalicular dilatation and elevation of the plasma bile salts, alkaline phosphatase, and cholesterol without a rise in bilirubin. Adaptation to the cholestatic injury occurred in about 60 days despite continued griseofulvin feeding. This was evidenced by decreased values in the biochemical profile with concomitant improvement in the bile canalicular morphology. Following this event of adaptation, Mallory bodies began to appear in the livers, often in the periphery of the hepatic lobule. This model may be useful in studying mechanisms of cholestasis, Mallory body formation, and their relationship to altered microtubular systems in the hepatocyte.

Alkaline Phosphatase↗
PubMed1978

Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis.

An acute phase of experimental autoimmune myasthenia gravis (EAMG) occurs transiently early in the immune response of Lewis rats to nicotinic acetylcholine receptors (AChR) when Bordetella pertussis is used as adjuvant. It is characterized by a destructive cellular attack directed at the postsynaptic membranes of muscle. Acute EAMG can be passively transferred to normal rats by IgG from serum of rats with chronic EAMG. In the present study, acute EAMG, induced either by passive transfer of syngeneic antibodies or by active immmunization, was inhibited in rats depleted of complement by treatment with cobra venom factor (CoF). Furthermore, passive transfer of antibodies in excess of the muscle's content of AChR was without any measurable effect in rats treated with CoF. Although 60% of the muscle's AChR was complexed with antibody, there was no reduction in the muscle's content of AChR, and neuromuscular transmission was not compromised as judged electromyographically by curare sensitivity. These data imply that redistribution, accelerated degradation, and impairment of the ionophore function of AChR, effects of antibodies described in vitro on extrajunctional AChR, do not play a significant role in vivo in impairing neuromuscular transmission in an intact neuromuscular junction. Complement appears to be a critical mediator of anti-AChR antibodies' pathogenicity in vivo.

Animals↗
PubMed1978

Preparation of lymphoid cells from small specimens of human gastrointestinal mucosa.

Several methods for the preparation of cell suspensions from human gastrointestinal mucosa were investigated. Satisfactory suspensions were obtained by incubating tissue fragments in a solution of collagenase and hyaluronidase overnight at 4 degrees C followed by 30 minutes at 37 degrees C. The resulting suspension contained large numbers of intact lymphoid cells; in addition, variable amounts of epithelial cells and cell debris were present. A high proportion of the lymphoid cells were shown by immunofluorescence to contain immunoglobulin (mainly IgA). Viability of these cells was demonstrated by dye exclusion, their ability to survive in short-term culture, and their ability to incorporate radio-labelled amino acid into immunoglobulin in vitro.

Cell Separation↗