Biomedical subjects

D B Lacy

Publications and source records attributed to D B Lacy.

75 records · Page 5Linked to original sources

PubMed1984

Effects of morphine on glucose homeostasis in the conscious dog.

This study was designed to assess the effects of morphine sulfate on glucose kinetics and on glucoregulatory hormones in conscious overnight fasted dogs. One group of experiments established a dose-response range. We studied the mechanisms of morphine-induced hyperglycemia in a second group. We also examined the effect of low dose morphine on glucose kinetics independent of changes in the endocrine pancreas by the use of somatostatin plus intraportal replacement of basal insulin and glucagon. In the dose-response group, morphine at 2 mg/h did not change plasma glucose, while morphine at 8 and 16 mg/h caused a hyperglycemic response. In the second group of experiments, morphine (16 mg/h) caused an increase in plasma glucose from a basal 99 +/- 3 to 154 +/- 13 mg/dl (P less than 0.05). Glucose production peaked at 3.9 +/- 0.7 vs. 2.5 +/- 0.2 mg/kg per min basally, while glucose clearance declined to 1.7 +/- 0.2 from 2.5 +/- 0.1 ml/kg per min (both P less than 0.05). Morphine increased epinephrine (1400 +/- 300 vs. 62 +/- 8 pg/ml), norepinephrine (335 +/- 66 vs. 113 +/- 10 pg/ml), glucagon (242 +/- 53 vs. 74 +/- 14 pg/ml), insulin (30 +/- 9 vs. 10 +/- 2 microU/ml), cortisol (11.1 +/- 3.3 vs. 0.9 +/- 0.2 micrograms/dl), and plasma beta-endorphin (88 +/- 27 vs. 23 +/- 6 pg/ml); all values P less than 0.05 compared with basal. These results show that morphine-induced hyperglycemia results from both stimulation of glucose production as well as inhibition of glucose clearance. These changes can be explained by rises in epinephrine, glucagon, and cortisol. These in turn are part of a widespread catabolic response initiated by high dose morphine that involves activation of the sympathetic nervous system, the endocrine pancreas, and the pituitary-adrenal axis. Also, we report the effect of a 2 mg/h infusion of morphine on glucose kinetics when the endocrine pancreas is clamped at basal levels. Under these conditions, morphine exerts a hypoglycemic effect (25% fall in plasma glucose, P less than 0.05) that is due to inhibition of glucose production (by 25-43%, P less than 0.05). The hypoglycemia was independent of detectable changes in insulin, glucagon, epinephrine and cortisol, and was not reversed by concurrent infusion of a slight molar excess of naloxone. Therefore, we postulate that the hypoglycemic effect of morphine results from the interaction of the opiate with non-mu receptors either in the liver or the central nervous system.

Animals↗

PubMedDate not supplied

Disposition of a mixed meal by conscious dogs after seven days of treatment with cyclosporine A and prednisone.

BACKGROUND: Combination immunosuppressive therapy, that often includes prednisone and cyclosporine A (CyA), is commonly used in the treatment of organ transplant patients. We hypothesized that CyA and prednisone treatment would alter the roles of the liver and peripheral tissues in the disposal of carbohydrates from a meal. METHODS: Using the arteriovenous difference technique, we examined the disposition of an intragastrically delivered mixed meal in eight 24-hour fasted conscious dogs that had received CyA 15 mg x kg(-1) daily and prednisone 5 mg twice daily for 7 consecutive days before study (CyA-prednisone group). The results were compared with those from a group of 13 dogs (control group) receiving the same meal but no drugs. RESULTS: Neither arterial blood glucose concentrations nor arterial plasma insulin or glucagon concentrations differed significantly between the groups at any time. Cumulative net gut glucose output was equivalent to 43 +/- 9 vs 57% +/- 7% of the glucose in the meal in CyA-prednisone vs control (p = .12). The CyA-prednisone group exhibited greater (p < .05) mean net hepatic glucose uptakes (15.4 +/- 4.6 vs 4.3 +/- 2.2 micromol x kg(-1) x min(-1) and net hepatic fractional extractions of glucose (7.8 +/- 1.6 and 1.5% +/- 1.0%) than the control group. Arterial blood lactate concentrations and net hepatic lactate output were greater in the CyA-prednisone group than the control group (p < .05). Hepatic glycogen content at the end of the study was 2.5-fold greater in the CyA-prednisone group than in the control group (p < .05). The nonhepatic tissues disposed of approximately 91% of the absorbed glucose in the control group but only approximately 26% in the CyA-prednisone group (p < .05). CONCLUSIONS: CyA-prednisone treatment caused a marked shift in the carbohydrate disposal from a meal, enhancing the hepatic glucose uptake and decreasing peripheral glucose disposal.

Alanine↗

PubMedDate not supplied

Impact of enteral and parenteral nutrition on hepatic and muscle glucose metabolism.

Liver and muscle metabolism were assessed in dogs adapted to long-term total parenteral (TPN) and enteral (TEN) nutrition. Studies were done in 13 conscious long-term catheterized dogs in which sampling (artery, portal and hepatic vein, and iliac vein), infusion catheters (inferior vena cava, duodenum), and transonic flow probes (hepatic artery, portal vein, and iliac artery) were implanted. Fourteen days after surgery dogs were grouped to receive TPN or TEN. After 5 days of TPN/TEN, substrate balances across the liver and limb were assessed. The liver was a marked net consumer of glucose in both groups (23.6 +/- 3.3 vs 22.6 +/- 2.8 micromol x kg(-1) x min(-1), TPN vs TEN) despite near normoglycemia (6.5 +/- 0.3 vs 6.7 +/- 0.2 mmol/L). Arterial insulin levels were higher during TEN (96 +/- 6 vs 144 +/- 30 pmol/L; p < .05). The majority (79 +/- 13 vs 76% +/- 7%) of the glucose taken up by the liver was released as lactate. Despite higher insulin levels during TEN the nonsplanchnic tissues consumed a lessor quantity of glucose (25.9 +/- 3.3 vs 16.1 +/- 3.9 micro x mol x kg(-1) x min(-1)). In summary, the liver undergoes a profound adaptation to TPN and TEN making it a major site of glucose uptake and conversion to lactate irrespective of the route of nutrient delivery. However, the insulin requirements are higher with TEN possibly secondary to impaired peripheral glucose removal.

Alanine↗