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A B Jenkins

Publications and source records attributed to A B Jenkins.

63 records · Page 4Linked to original sources
PubMed1986

2-deoxy-D-glucose metabolism in individual tissues of the rat in vivo.

The nature of and rates of loss of products of systemic radiolabelled 2-deoxy-D-glucose in rat tissues in vivo were investigated to validate the use of this tracer to measure rates of metabolism of circulating glucose by tissues in vivo. Apparent first order rate constants for loss of products ranged from 8.0 +/- 0.10 (SD) X 10(-3) min-1 (liver) to 2.2 +/- 0.8 X 10(-3) min-1 (skeletal muscle). 2-deoxyglucose 6-phosphate was the major product found in all tissues examined except liver; all tissues contained other minor products. Products were effectively trapped by rat tissues in vivo allowing the use of this tracer for the measurement of rates of circulating glucose utilisation by tissues in vivo.

Animals↗
PubMed1986

Regulation of hepatic glucose output during exercise by circulating glucose and insulin in humans.

We have tested the hypothesis that hepatic glucose output (Ra) during exercise in humans is subject to feedback control by circulating glucose within a control range that is determined by the circulating insulin concentration. Three exercise protocols based on 60-min cycle ergometer exercise at 55% maximal O2 consumption were used: 1) control, 2) insulin infusion with a euglycemic clamp, and 3) insulin infusion with a fixed-rate glucose infusion. Ra was measured using a constant infusion of [3H]glucose. During the glucose clamp there was no Ra response to exercise. There were significant inverse relationships between Ra and plasma glucose during control exercise (r = -0.73, P less than 0.001) and exercise with fixed-rate glucose and insulin infusion (r = -0.96, P less than 0.001). During the fixed-rate glucose and insulin infusion, plasma glucose fell from the commencement of exercise but stabilized at a lower level. These results are interpreted in terms of a simple difference controller where Ra is proportional to the deviation of plasma glucose from a defined set point. Insulin affects Ra and regulates the steady-state glucose level by altering the sensitivity of this control system.

Adult↗
PubMed1985

Exercise-induced hepatic glucose output is precisely sensitive to the rate of systemic glucose supply.

It has previously been established that a glucose infusion causing hyperglycemia and alterations in the levels of glucoregulatory hormones suppresses the exercise-induced increment in systemic glucose appearance (Ra). In an attempt to define the mechanisms responsible for this suppression of Ra, five normal subjects were exercised for 60 minutes on a bicycle ergometer at 60% Vo2 max on two occasions. On both occasions Ra was measured by a nonsteady state technique using a constant infusion of 3-3H-glucose. On the second occasion, an IV infusion of glucose was administered in a stepwise fashion to simulate in timing and magnitude the measured Ra response from the first study. Endogenous glucose production in the second study, estimated by subtracting the amount of glucose infused from the measured Ra response, did not increase above basal (endogenous glucose output response = 0.5 +/- 8.4 mmol/60 min v control study 60.2 +/- 6.6 mmol/60 min, P less than 0.01). The suppression of Ra was associated with a small but significant effect on venous plasma glucose (increment above basal less than 0.3 mmol/L, P less than 0.05) and a significant change in glucose metabolic clearance rate during the second 30 minutes of exercise. Serum insulin, C-peptide, cortisol, growth hormone, and plasma glucagon responses to exercise were not significantly affected by glucose infusion and the ratio of circulating insulin to glucagon was also not affected. These results indicate that hepatic glucose output during exercise is precisely sensitive to glucose supply. The feedback inhibition is presumably mediated by a small increase in plasma glucose but cannot readily be accounted for by changes in glucoregulatory hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Dose-response curves for in vivo insulin sensitivity in individual tissues in rats.

A technique is described for examining in vivo insulin action on glucose utilization in individual tissues in the intact conscious rat. Indices of tissue glucose metabolic rate Rg' and of the percentage of total glucose uptake incorporated into specific storage products (Cf) are derived from tissue analysis after bolus administration of 2-[3H]deoxyglucose and [14C]glucose during the plateau phase of the euglycemic clamp. The effects of insulin elevation have been examined in several tissues. Rg' in diaphragm increased 10-fold over basal (maximal) with a half-maximal sensitivity (ED50) of 150 mU/l. This was similar to the ED50 for net whole body glucose utilization of 133 mU/l. In adipose tissue Rg' increased by twofold and Cf into lipids by sixfold; both were near maximal at 150 mU/l (ED50 of 60 mU/l). A small but significant insulin effect (Rg' increased 2-fold) was found in lung. Insulin did not significantly increase Cf into total liver lipids or glycogen. The methodology described here significantly increases the usefulness of the glucose clamp technique in the study of insulin action. Dose-response curves for insulin action during the euglycemic clamp vary considerably among different target tissues in the rat.

Adipose Tissue↗
PubMed1985

Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats.

The euglycemic hyperinsulinemic clamp technique in conscious unrestrained rats was used to examine the effect of insulin on glucose metabolism in metabolically distinct skeletal muscle in vivo. Tissue glucose metabolic rate (R'g) was estimated using 2-[3H]-deoxyglucose, and glucose disposal was examined by measuring glycogen content and [14C]glucose incorporation into glycogen in four different muscles. Insulin sensitivity varied among different muscle types in that the insulin concentration required for half-maximal stimulation of R'g was 80, 150, 280, and 320 mU/1 for soleus (SOL), red gastrocnemius (RG), white gastrocnemius (WG), and extensor digitorum longus, respectively. There were similar relative differences in the maximal effect of insulin on R'g in these muscles. Maximal insulin stimulation almost doubled muscle glycogen content in RG and SOL, whereas there was no change in WG. The relationship between R'g and glycogen synthesis indicated that increased glucose uptake resulted predominantly in glycogen storage. There was an excellent relationship between maximal R'g and blood flow in different muscles. We conclude that there is marked heterogeneity in insulin sensitivity and responsiveness among muscles of different fiber composition. Insulin-induced increases in total peripheral glucose disposal occur predominantly in muscles containing a high proportion of oxidative fibers. Therefore the relative proportion of oxidative to glycolytic muscle fibers may be important factors in determining whole body insulin sensitivity.

Animals↗
PubMed1984

Effect of contact material on vibration-induced insulin aggregation.

The tendency of insulin to form insoluble aggregates is a major obstacle to the development of implantable insulin infusion systems for treatment of insulin-deficient diabetic patients. A test system was developed to examine the kinetics of insulin aggregation under controlled conditions of temperature, vibration and contact material in an effort to provide design criteria for minimising aggregation. The contact materials tested were all potentially suitable for pump reservoirs on engineering criteria and included metals (stainless steel, titanium and a titanium alloy) and various plastics (polypropylene, polytetrafluoroethylene, polyvinylchloride, polyamide, cellulose butyrate and silicone elastomer). The rate of insulin aggregation was markedly affected by the nature of the contact material. Hydrophilic materials, particularly polyamide and cellulose butyrate (2% of total insulin aggregated after 96 h vibration), appeared more compatible with insulin stability than did hydrophobic ones, such as polypropylene (16% aggregation) and polyvinylchloride (37% aggregation). A specially formulated 'pump' insulin preparation, stabilised by addition of polyethylenepolypropyleneglycol, was significantly superior (three to five times more stable) to a regular neutral insulin formulation under most, but not all, conditions. Standard clinical syringes (polypropylene) performed poorly with both insulin formulations but especially with the neutral regular insulin (100% aggregation after 96 h vibration). In addition to physical aggregates, significant amounts (5%-30%) of the insulin remaining in solution were no longer detectable by immuno- or receptorassay in all materials tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗
PubMed1981

Insulin precipitation in artificial infusion devices.

Precipitation of insulin is a problem with mechanical insulin infusion devices. Therefore conditions affecting insulin precipitation have been studied in a recirculating system using a peristaltic pump. Acetate buffer favoured precipitation and a pH of 2, 3 or 8 resulted in no less (and often more) precipitation than a pH of 7 using either acetate of phosphate buffer. However, no precipitation occurred in a phosphate buffered neutral preparation after ten days of pumping through tubing pretreated with EDTA. In comparison at pH 7, using acetate buffer with untreated tubing, more than 95% of insulin was precipitated in ten days. A heavy metal-insulin association appears to be a major factor in the precipitation. However, some formation of insulin fibrils is probable as the precipitate is autocatalytic and partially acid insoluble. Phosphate buffered highly purified porcine insulin is suitable for relatively prolonged infusion if metal ion contamination of the delivery system is minimised.

Buffers↗