Metabolic characteristics of cat kidney: failure to adapt to metabolic acidosis

During studies performed on domestic cats made acidotic with ammonium chloride, it was found that the cat kidney is unable to adapt to metabolic acidosis. Renal proximal tubules do not increase their production of ammonia or glucose from glutamine during acidosis. During in vivo studies, the renal excretion of ammonia did not change much during acidosis. Other metabolic parameters in the cat were not very different from those found in other animals such as rat or dog. However, it was found that cats may show a relatively high plasma glucose concentration compared with other animals. Plasma insulin concentration was normal, and the animals showed no evidence of diabetes mellitus. It is not known whether limitation of ammoniagenesis and elevated plasma glucose concentration also characterize larger felidae such as panthers and cougars.

Download Full-text

Effect of Halothane Anesthesia on Glucose Utilization and Production in Adolescents

Anesthesiology ◽

10.1097/00000542-199505000-00010 ◽

1995 ◽

Vol 82 (5) ◽

pp. 1154-1159 ◽

Cited By ~ 12

Author(s):

Dounia Sbai ◽

Philippe Jouvet ◽

Anne Soulier ◽

Luc Penicaud ◽

Jacques Merckx ◽

...

Keyword(s):

Plasma Glucose ◽

Glucose Concentration ◽

Glucose Utilization ◽

Blood Glucose Concentration ◽

Glucose Infusion ◽

Plasma Glucose Concentration ◽

Whole Body ◽

Metabolic Clearance ◽

Halothane Anesthesia ◽

Plasma Insulin Concentration

Background It should be possible to avoid variations in plasma glucose concentration during anesthesia by adjusting glucose infusion rate to whole-body glucose uptake. To study this hypothesis, we measured glucose utilization and production, before and during halothane anesthesia. Methods After an overnight fast, six adolescents between 12 and 17 yr of age were infused with tracer doses of [6,6-2H2]glucose for 2 h before undergoing anesthesia, and the infusion was continued after induction, until the beginning of surgery. Plasma glucose concentration was monitored throughout, and free fatty acids, lactate, insulin, and glucagon concentrations were measured before and during anesthesia. Results Despite the use of a glucose-free maintenance solution, plasma glucose concentration increased slightly but significantly 5 min after induction (5.3 +/- 0.4 vs. 4.5 +/- 0.4 mmol.l-1, P < 0.05). This early increase corresponded to a significant increase in endogenous glucose production over basal conditions (4.1 +/- 0.4 vs. 3.6 +/- 0.2 mg.kg-1.min-1, P < 0.05), with no concomitant change in peripheral glucose utilization. Fifteen minutes after induction, both glucose utilization and production rates decreased steadily and were 20% less than basal values by 35 min after induction (2.9 +/- 0.3 vs. 3.6 +/- 0.2 mg.kg-1.min-1, P < 0.05). Similarly, glucose metabolic clearance rate decreased by 25% after 35 min. Despite the increase in blood glucose concentration, anesthesia resulted in a significant decrease in plasma insulin concentration. Conclusions These data suggest that halothane anesthesia per se affects glucose metabolism. The decrease in peripheral glucose utilization and metabolic clearance rates and the blunted insulin release question the relevance of glucose infusion in these clinical settings.

Download Full-text

Orally administered, insulin-loaded amidated pectin hydrogel beads sustain plasma concentrations of insulin in streptozotocin-diabetic rats

Journal of Endocrinology ◽

10.1677/joe.0.1640001 ◽

2000 ◽

Vol 164 (1) ◽

pp. 1-6 ◽

Cited By ~ 39

Author(s):

CT Musabayane ◽

O Munjeri ◽

P Bwititi ◽

EE Osim

Keyword(s):

Plasma Glucose ◽

Glucose Concentration ◽

Plasma Insulin ◽

Plasma Concentrations ◽

Diabetic Rats ◽

Plasma Glucose Concentration ◽

Pharmacokinetic Parameters ◽

Plasma Insulin Concentration ◽

Hydrogel Beads ◽

Concomitant Reduction

We report successful oral administration of insulin entrapped in amidated pectin hydrogel beads in streptozotocin (STZ)-diabetic rats, with a concomitant reduction in plasma glucose concentration. The pectin-insulin (PI) beads were prepared by the gelation of humilin-pectin solutions in the presence of calcium. Separate groups of STZ-diabetic rats were orally administered two PI beads (30 micrograms insulin) once or twice daily or three beads (46 micrograms) once daily for 2 weeks. Control non-diabetic and STZ-diabetic rats were orally administered pectin hydrogel drug-free beads. By comparison with control non-diabetic rats, untreated STZ-diabetic rats exhibited significantly low plasma insulin concentration (0.32+/-0. 03 ng/ml, n=6, compared with 2.60+/-0.44 ng/ml in controls, n=6) and increased plasma glucose concentrations (25.84+/-1.44 mmol/l compared with 10.72+/- 0.52 mmol/l in controls). Administration of two PI beads twice daily (60 micrograms active insulin) or three beads (46 micrograms) once a day to STZ-diabetic rats increased plasma insulin concentrations (0.89+/-0.09 ng/ml and 1.85+/- 0.26 ng/ml, respectively), with a concomitant reduction in plasma glucose concentration (15.45+/-1.63 mmol/l and 10.56+/-0.26 mmol/l, respectively). However, a single dose of PI beads (30 micrograms) did not affect plasma insulin concentrations, although plasma glucose concentrations (17.82+/-2.98 mmol/l) were significantly reduced compared with those in untreated STZ-diabetic rats. Pharmacokinetic parameters in STZ-diabetic rats show that the orally administered PI beads (30 micrograms insulin) were more effective in sustaining plasma insulin concentrations than was s.c. insulin (30 micrograms). The data from this study suggest that this insulin-loaded amidated pectin hydrogel bead formulation not only produces sustained release of insulin, but may also reduce plasma glucose concentration in diabetes mellitus.

Download Full-text

Glucose intolerance following chronic metabolic acidosis in man.

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1979.236.4.e328 ◽

1979 ◽

Vol 236 (4) ◽

pp. E328 ◽

Cited By ~ 3

Author(s):

R A DeFronzo ◽

A D Beckles

Keyword(s):

Metabolic Acidosis ◽

Glucose Metabolism ◽

Plasma Glucose ◽

Glucose Concentration ◽

Plasma Insulin ◽

Glucose Infusion ◽

Insulin Concentration ◽

Plasma Insulin Concentration ◽

Chronic Metabolic Acidosis ◽

Tissue Sensitivity

The effect of chronic metabolic acidosis (0.1 g/(kg . day) X 3 days) on carbohydrate metabolism was examined with the glucose-clamp technique in 16 healthy volunteers. Hyperglycemic clamp. Plasma glucose concentration is acutely raised and maintained 125 mg/dl above the basal level. Because the glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism (M). Following NH4Cl, M decreased from 8.95 +/- 1.12 to 7.35 +/- 0.76 (P less than 0.05) despite an increased plasma insulin concentration (I) 23 +/- 9%, P less than 0.05). Consequently the M/I ratio, an index of tissue sensitivity to insulin, decreased by 32 +/- 5% (P less than 0.005). Euglycemic clamp. Plasma insulin concentration is acutely raised and maintained 101 +/- 3 microU/ml above basal and plasma glucose is held constant at the fasting level by a variable glucose infusion (M). Following NH4Cl both M and M/I decreased by 15 +/- 4% (P = 0.005) and 15 +/- 5% (P = 0.01), respectively. Metabolic acidosis had no effect on basal [3-3H]glucose production or the percent of decline (91 +/- 4%) following hyperinsulinemia. Both hyperglycemic and euglycemic clamp studies indicate that impaired glucose metabolism following metabolic acidosis results from impaired tissue sensitivity to insulin.

Download Full-text

Postprandial glucose and insulin profiles following a glucose-loaded meal in cats and dogs

British Journal Of Nutrition ◽

10.1017/s0007114511000857 ◽

2011 ◽

Vol 106 (S1) ◽

pp. S101-S104 ◽

Cited By ~ 15

Author(s):

Adrian K. Hewson-Hughes ◽

Matthew S. Gilham ◽

Sarah Upton ◽

Alison Colyer ◽

Richard Butterwick ◽

...

Keyword(s):

Body Weight ◽

Plasma Glucose ◽

Test Meal ◽

Glucose Concentration ◽

Plasma Insulin ◽

Plasma Glucose Concentration ◽

Insulin Concentration ◽

Metabolic Adaptation ◽

Plasma Insulin Concentration ◽

High Blood Glucose

Data from intravenous (i.v.) glucose tolerance tests suggest that glucose clearance from the blood is slower in cats than in dogs. Since different physiological pathways are activated following oral administration compared with i.v. administration, we investigated the profiles of plasma glucose and insulin in cats and dogs following ingestion of a test meal with or without glucose. Adult male and female cats and dogs were fed either a high-protein (HP) test meal (15 g/kg body weight; ten cats and eleven dogs) or a HP+glucose test meal (13 g/kg body-weight HP diet+2 g/kg body-weight d-glucose; seven cats and thirteen dogs) following a 24 h fast. Marked differences in plasma glucose and insulin profiles were observed in cats and dogs following ingestion of the glucose-loaded meal. In cats, mean plasma glucose concentration reached a peak at 120 min (10·2, 95 % CI 9·7, 10·8 mmol/l) and returned to baseline by 240 min, but no statistically significant change in plasma insulin concentration was observed. In dogs, mean plasma glucose concentration reached a peak at 60 min (6·3, 95 % CI 5·9, 6·7 mmol/l) and returned to baseline by 90 min, while plasma insulin concentration was significantly higher than pre-meal values from 30 to 120 min following the glucose-loaded meal. These results indicate that cats are not as efficient as dogs at rapidly decreasing high blood glucose levels and are consistent with a known metabolic adaptation of cats, namely a lack of glucokinase, which is important for both insulin secretion and glucose uptake from the blood.

Download Full-text

Insulin does not mediate the attenuation of fatigue associated with glucose infusion in rat plantaris muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.00040.2003 ◽

2003 ◽

Vol 95 (1) ◽

pp. 330-335 ◽

Cited By ~ 8

Author(s):

Antony D. Karelis ◽

François Péronnet ◽

Phillip F. Gardiner

Keyword(s):

Plasma Glucose ◽

Glucose Concentration ◽

Plasma Insulin ◽

Glucose Infusion ◽

Plasma Glucose Concentration ◽

Muscle Performance ◽

Insulin Concentration ◽

Dynamic Force ◽

Plantaris Muscle ◽

Plasma Insulin Concentration

Glucose infusion attenuates fatigue in rat plantaris muscle stimulated in situ, and this is associated with a better maintenance of electrical properties of the fiber membrane (Karelis AD, Péronnet F, and Gardiner PF. Exp Physiol 87: 585–592, 2002). The purpose of the present study was to test the hypothesis that elevated plasma insulin concentration due to glucose infusion (∼900 pmol/l), rather than high plasma glucose concentration (∼10–11 mmol/l), could be responsible for this phenomenon, because insulin has been shown to stimulate the Na+-K+ pump. The plantaris muscle was indirectly stimulated (50 Hz, for 200 ms, 5 V, every 2.7 s) via the sciatic nerve to perform concentric contractions for 60 min, while insulin (8 mU · kg-1 · min-1: plasma insulin ∼900 pmol/l) and glucose were infused to maintain plasma glucose concentration between 4 and 6 [6.2 ± 0.4 mg · kg-1 · min-1: hyperinsulinemic-euglycemic (HE)] or 10 and 12 mmol/l [21.7 ± 1.1 mg · kg-1 · min-1: hyperinsulinemic-hyperglycemic clamps (HH)] (6 rats/group). The reduction in submaximal dynamic force was significantly ( P < 0.05) less with HH (-53%) than with HE and saline only (-66 and -70%, respectively). M-wave characteristics were also better maintained in the HH than in HE and control groups. These results demonstrate that the increase in insulin concentration is not responsible for the increase in muscle performance observed after the elevation of circulating glucose.

Download Full-text

2-Deoxy-D-glucose transport in dog kidney

AJP Renal Physiology ◽

10.1152/ajprenal.1982.242.6.f711 ◽

1982 ◽

Vol 242 (6) ◽

pp. F711-F720

Author(s):

M. Silverman ◽

R. J. Turner

Keyword(s):

Plasma Glucose ◽

Glucose Concentration ◽

Indicator Dilution ◽

Plasma Glucose Concentration ◽

Kidney Cortex ◽

Multiple Indicator Dilution ◽

Carrier Mechanism ◽

Dog Kidney

Osmotically active brush border membrane (BBM) and antiluminal membrane (ALM) vesicles prepared from dog kidney cortex were used to investigate transport of 2-deoxy-D-glucose (2DG). A parallel in vivo study was carried out using the pulse-injection multiple indicator-dilution technique. Single-pass indicator-dilution experiments demonstrate both luminal and antiluminal interactions for 2DG. The antiluminal interaction is blocked by large systemic doses of phlorizin (100-200 mg/kg). With plasma glucose concentration in the range of 4-5 mM fractional luminal extraction of 2-[14C]DG relative to simultaneously filtered creatinine is 25 +/- 2%. This luminal extraction can be inhibited by raising plasma glucose concentration to approximately 30 mM and by administration of low systemic doses of phlorizin (6-8 mg/Kg). 2DG uptake into BBM vesicles equilibrates into the same intravesicular volume as D-glucose. A definite Na+ component of 2DG uptake can be defined which is more sensitive to inhibition by phlorizin than by phloretin and is also inhibited by D-glucose and alpha-methyl-D-glucoside but not by L-glucose. But compared with D-glucose, the Na+-dependent BBM uptake of 2DG is greatly reduced. 2DG uptake into ALM vesicles is independent of Na+, is more sensitive to inhibition by phloretin than by phlorizin, and is also blocked by cytochalasin B but not by alpha-methyl-D-glucoside. Influx of 2-[14C] DG into ALM vesicles is increased by preloading with unlabeled D-glucose. Conversely influx of D[14C]glucose into ALM vesicles is accelerated by preloading with unlabeled 2DG. ALM influx of radiolabeled 2DG is accelerated by D-glucose, 3-O-methyl-D-glucose, D-galactose, and unlabeled 2DG but not by alpha-methyl-D-glucoside. The specificity of inhibition and countertransport results from in vivo and in vitro experiments are consistent with the proposal that 2DG shares a common carrier mechanism with D-glucose at each of the opposing membrane surfaces.

Download Full-text

Betacellulin improves glucose metabolism by promoting conversion of intraislet precursor cells to β-cells in streptozotocin-treated mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00120.2003 ◽

2003 ◽

Vol 285 (3) ◽

pp. E577-E583 ◽

Cited By ~ 40

Author(s):

Lei Li ◽

Masaharu Seno ◽

Hidenori Yamada ◽

Itaru Kojima

Keyword(s):

Glucose Metabolism ◽

Plasma Glucose ◽

Glucose Concentration ◽

Experimental Diabetes ◽

Islet Cells ◽

Plasma Glucose Concentration ◽

High Dose ◽

Β Cells ◽

Plasma Insulin Concentration ◽

Severe Diabetes

Betacellulin (BTC) induces differentiation of pancreatic β-cells and promotes regeneration of β-cells in experimental diabetes. The present study was conducted to determine if BTC improved glucose metabolism in severe diabetes induced by a high dose of streptozotocin (STZ) in mice. Male ICR mice were injected with 200 μg/g ip STZ, and various doses of BTC were administered daily for 14 days. The plasma glucose concentration increased to a level of >500 mg/dl in STZ-injected mice. BTC (0.2 μg/g) significantly reduced the plasma glucose concentration, but a higher concentration was ineffective. The effect of BTC was marked by day 4 but became smaller on day 6 or later. The plasma insulin concentration and the insulin content were significantly higher in mice treated with 0.1 and 0.2 μg/g BTC. BTC treatment significantly increased the number of β-cells in each islet as well as the number of insulin-positive islets. Within islets, the numbers of 5-bromo-2-deoxyuridine/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells were significantly increased by BTC. These results indicate that BTC improved hyperglycemia induced by a high dose of STZ by promoting neoformation of β-cells, mainly from somatostatin-positive islet cells.

Download Full-text

Glucose clamp technique: a method for quantifying insulin secretion and resistance.

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1979.237.3.e214 ◽

1979 ◽

Vol 237 (3) ◽

pp. E214 ◽

Cited By ~ 548

Author(s):

R A DeFronzo ◽

J D Tobin ◽

R Andres

Keyword(s):

Negative Feedback ◽

Plasma Glucose ◽

Glucose Concentration ◽

Plasma Insulin ◽

Glucose Infusion ◽

Plasma Glucose Concentration ◽

Plasma Insulin Concentration ◽

Clamp Technique ◽

Hyperglycemic Clamp ◽

Tissue Sensitivity

Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.

Download Full-text