Primed-continuous infusion of [2-3H]- and [U-14C]lactate was used to study the effects of endurance training (running 2 h/day at 29.4 m/min up a 15% gradient) on lactate metabolism in rats. Measurements were made under three metabolic conditions: rest (Re), easy exercise (EE, 13.4 m/min, 1% gradient) and hard exercise (HE, 26.8 m/min, 1% gradient). Blood lactate levels in trained animals increased from 1.0 +/- 0.09 mM in Re to 1.64 +/- 0.21 in EE and 2.66 +/- 0.38 in HE. Control animals also demonstrated an increase in blood lactate with increasing work rate, but values were 1.93 +/- 0.21 and 4.62 +/- 0.57 mM at EE and HE, respectively. Lactate turnover rates (RtLA) measured with [U-14C]lactate increased from 214.0 +/- 17.0 mumol.kg-1.min-1 in Re to 390.3 +/- 31.6 in EE and 518.1 +/- 56.4 in HE. No significant differences in RtLA were observed between controls and trained animals under any condition. Identical relationships between RtLA and exercise or training were obtained with [2-3H]lactate; however, the values obtained were consistently 90% higher than those observed with [U-14C]lactate. Metabolic clearance rate (MCR) for 14C was not significantly different in Re between controls and trained animals (180.6 +/- 27.7 ml.kg-1.min-1). Metabolic clearance of lactate in trained animals was 37 and 107% greater than in controls during EE and HE, respectively. Results indicate that the effect of endurance training is not on production of lactate but on its clearance from the blood.

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Glucose is the primary fuel for the vast majority of cells, and animals have evolved essential cellular, autonomic, endocrine, and behavioral measures to counteract both hypo-and hyperglycemia. A central component of these counterregulatory mechanisms is the ability of specific sensory elements to detect changes in blood glucose and then use that information to produce appropriate counterregulatory responses. Here we focus on the organization of the neural systems that are engaged by glucosensing mechanisms when blood glucose concentrations fall to levels that pose a physiological threat. We employ a classic sensori-motor integrative schema to describe the peripheral, hindbrain, and hypothalamic components that make up counterregulatory mechanisms in the brain. We propose that models previously developed to describe how the forebrain modulates autonomic reflex loops in the hindbrain offer a reasoned framework for explaining how counterregulatory neural mechanisms in the hypothalamus and hindbrain are structured.

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We sought to elucidate the role of the portal vein a fferents in the sympathetic response to hypoglycemia. Laparotomy was performed on 27 male Wi s t a r rats. Portal veins were painted with either 90% phenol (denervation group [PDN]) or 0.9% saline solution (sham-operated group [SHAM]). Rats were chronically cannulated in the carotid artery (sampling), jugular vein (infusion), and portal vein (infusion). After a recovery period of 5 days, animals were exposed to a hyperinsulinemic-hypoglycemic clamp, with glucose infused either portally (POR) or peripherally (PER). In all animals, systemic hypoglycemia (2.48 ± 0 . 0 9 mmol/l) was induced via jugular vein insulin infusion (50 mU · k g -1 · min -1 ). Arterial plasma catecholamines were assessed at basal (-30 and 0 m i n ) and during sustained hypoglycemia (60, 75, 90, and 105 min). By design, portal vein glucose concentrations were significantly elevated during POR versus PER (4.4 ± 0.14 vs. 2.5 ± 0.07 mmol/l; P < 0.01, respectively) for both PDN and SHAM. There were no significant differences in arterial glucose or insulin concentration between the four experimental conditions at any point in time. When portal glycemia and systemic glycemia fell concomitantly (SHAM-PER), epinephrine increased 12-fold above basal (3.75 ± 0.34 and 44.56 ± 6.1 nmol/l; P < 0.001). However, maintenance of portal normoglycemia (SHAM-POR) caused a 50% suppression of the epinephrine response, despite cerebral hypoglycemia (22.2 ± 3.1 nmol/l, P < 0.001). Portal denervation resulted in a significant blunting of the sympathoadrenal response to whole-body hypoglycemia (PDN-PER 27.6 ± 3.8 nmol/l vs. SHAM-PER; P < 0.002). In contrast to the sham experiments, there was no further suppression in arterial epinephrine concentrations observed during PDN-POR versus PDN-PER (P = 0.8). These findings indicate that portal vein afferent innervation is critical for hypoglycemic detection and normal sympathoadrenal counterregulation. D i a b e t e s 4 9 :8-12, 2000 C atecholamines constitute the primary defense against hypoglycemia for individuals with type 1 diabetes, in which the ability to suppress insulin is absent and the capacity to secrete glucagon is diminished. The catecholamine response has been well characterized for both normal and diabetic individuals (1-4). Under normal conditions, this sympathetic response appears sufficient to compensate for the loss of other counterregulatory measures (1,2). Unfortunately, over time, the catecholamine response for individuals with type 1 diabetes diminishes relative to the fall in blood glucose (1,2). The diminished catecholamine response appears to have been further exacerbated by increasingly aggressive attempts to control blood glucose levels in type 1 diabetic patients (3,4).Although iatrogenic hypoglycemia has been invoked as a partial explanation, in general, the pathology of the diminished sympathetic response in patients with type 1 diabetes remains poorly understood. In part, this can be attributed to the lack of knowledge concerning the locus f...