Changes in insulin response to glucose after exercise training in partially pancreatectomized rats.

The effects of exercise training on glucose-stimulated insulin secretion (GSIS) were studied in male Sprague-Dawley rats made mildly to severely diabetic by partial pancreatectomy. Exercise trained (10 wk treadmill; T) and untrained (Unt) rats were grouped according to posttraining fed-state hyperglycemia as follows: T less than 200 and Unt less than 200 (glucose concn less than 200 mg/dl), T 200-300 and Unt 200-300 (glucose concn 200-300 mg/dl), and T greater than 300 and Unt greater than 300 (glucose concn greater than 300 mg/dl). After exercise training, hyperglycemic glucose clamps were performed in awake rats by elevation of arterial blood glucose concentration 126 mg/dl above fasting basal levels for 90 min. Exercise training significantly increased muscle citrate synthase activity. Prevailing hyperglycemia was reduced during the 10-wk exercise training period in all T rats with fed-state glucose concentrations less than 300, and only 53% of Unt rats in these groups had reduced glycemia. GSIS was significantly higher in T less than 200 [2.4 +/- 0.7 (SD) ng/ml at 90 min] than in Unt less than 200 (1.5 +/- 0.3). A similar response was found for T 200-300 (1.1 +/- 0.3 ng/dl) vs. Unt 200-300 (0.7 +/- 0.1) but not T greater than 300 (0.36 +/- 0.2) vs Unt greater than 300 (0.44 +/- 0.05). Sham-operated control rats had insulin concentrations of 6.6 +/- 1.6 ng/ml at the 90th min of the clamp. Acute exercise reduced fed-state glycemia in rats with mild-to-moderate (less than 300 mg/dl) diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetic parameters for plasma beta-endorphin in lean and obese Zucker rats.

To determine plasma clearance kinetics for beta-endorphin (BE) by empirical compartmental analysis, a bolus of radioactive labeled 125I-BE was rapidly injected into a carotid artery catheter of unanesthetized lean (L) and obese (O) Zucker rats. The plasma disappearance of 125I was followed over a 3-h period. A 3-component exponential equation provided the best fit for plasma data. Plasma transit times were very short (10 s); however, plasma fractional catabolic rate was much slower. Plasma mean residence time was similar for both groups (50 min) as was recycle time (1.3 min). These data suggest that BE plasma disappearance kinetics are similar in L and O rats.

Effect of training on insulin secretion from single pancreatic beta cells.

The objective of this study was to determine whether insulin secretion from single pancreatic beta cells is reduced by endurance training. Male Sprague Dawley rats either trained (T, N = 9) for 11 wk on a rodent treadmill, remained sedentary, and were fed ad libitum (S, N = 8) or remained sedentary and were food restricted (pair fed, PF, N = 8) so that final body weights were similar to T. After training, T had significantly higher red gastrocnemius muscle citrate synthase activity compared with S and PF. In vivo insulin secretion was lower in T (4.6 +/- 1.4 ng.ml-1, mean +/- SEM of 70' + 90' concentrations during a hyperglycemic glucose clamp) when compared with S, 8.1 +/- 1.6 and PF, 9.7 +/- 1.7 ng.ml-1. In vitro insulin secretion from single beta cells was measured using the cell blot assay (Kendall and Hymer, Endocrinology, 121:2260-2262, 1987) and T, had lower secretion 2.6 +/- 1.4 pg.cell-1 when compared (P less than 0.05) with S, 6.7 +/- 0.6, but not lower than PF, 4.1 +/- 1.7 pg.cell-1. These data suggest that some of the training-induced reduction in insulin secretory response to glucose may be attributable to changes within the beta cell itself.

A new injection technique for intracerebral drug administration in behaving animals.

A new fluid pump and technique has been described for drug administration into either ventricles or directly into brain tissue of awake, freely behaving animals. The novel apparatus and procedures eliminate most of the common methodological obstacles to injecting nl volume amounts into freely moving animals.

Endopeptidase 24.16B. A new variant of endopeptidase 24.16.

A peptidase, isolated from rat testes, is inhibited by 1 mM o-phenanthroline, 1 microM N-(1-(R,S)-carboxyl-3-phenylpropyl)-Ala-Ala-Phe-p-aminobenzoate, and 6 mM Pro-Ile, properties similar to those ascribed to endopeptidase 24.16. The enzyme hydrolyzes dynorphin A-8, neurotensin 1-13, angiotensin I, and substance P. Kinetic analysis of a series of angiotensin I analogs showed that substitutions at P-1, P-1', or P-2' had little effect on Km or Kcat. Variation of peptide size with a series of dynorphin A peptides showed chain length to be significant. The peptidase cleaved dynorphin A-8 at both Leu5-Arg6 and Arg6-Arg7, and neurotensin 1-13 at Pro10-Tyr11 and Arg8-Arg9. In contrast, rat endopeptidase 24.16 cleaves dynorphin A-8 at Gly4-Leu5 and Leu5-Arg6, and neurotensin 1-13 only at Pro10-Tyr11. These findings, as well as the observation that endopeptidase 24.16 exhibits a considerably higher affinity for Pro-Ile, Ki = 90 microM, indicates the peptidase isolated in this study is related to, but distinct from, rat endopeptidase 24.16. We propose that this new endopeptidase be referred to as endopeptidase 24.16B, while the originally described enzyme be referred to as endopeptidase 24.16A.

Influence of opioids in hypothalamic nuclei on cold thermogenesis of lean and obese LA/N-cp rats.

An overactive endogenous opioid peptide system (EOP) in the hypothalamus of the obese rats could contribute to a subnormal metabolic response to cold stress. Specific mu, delta, kappa opioid receptor antagonists and naloxone were infused into cannulaes aimed at the paraventricular nucleus (PVN) of awake freely moving obese (LA/N-cp corpulent) and lean littermate rats. Metabolic responses were measured by indirect calorimetry during thermoneutrality (30 degrees C) and at 10 degrees C for 60 minutes each. When expressed relative to metabolic body size (kg(-.75)) obese rats had lower values (obese = 21.1 +/- 1.9 vs. lean = 27.9 +/- 2.7 ml x kg(-.75) x min, mean +/- s.d., p < 0.05) at 10 degrees C during saline infusion. EOP antagonist infusions at 30 degrees C had no effect on metabolic rate for either lean or obese animals. Mu (23.5 +/- 3.4 ml x kg x (-75) x min) and delta (23.0 +/- 2.0) antagonism and naloxone (25.0 +/- 2.3) significantly increased the metabolic response to cold in obese but not lean rats. These data suggest that certain subtypes of EOP receptors in or near PVN are overactive in obese rats. This overactive state may inappropriately inhibit the thermogenic response to cold stress in obesity.