A B S T R A C T The effects of stimulation of the mixed autonomic nerve to the dog pancreas has been studied under conditions in which both pancreaticoduodenal vein blood flow and insulin concentration were determined. Stimulation resulted in increased insulin output, which was blocked by prior administration of atropine. Blood flow was reduced by stimulation in proportion to the rate of stimulation. At 40 stimuli/s a maximum effect was found at 1 min with a gradual return toward base line despite continued application of the stimulus. Atropinization had no effect on blood flow changes. Insulin responses to 0.1 g/kg glucose were reduced on the average 40% by simultaneous stimulation of the pancreatic nerve at 40 cycles/s in atropinized animals. These studies establish this preparation as a reproducible model for the direct examination of autonomic influences on endocrine pancreatic function. From them it is concluded that the nerve supply to the endocrine pancreas of the dog is sufficient to inhibit insulin secretion by activation of the sympathetic nerves and to stimulate insulin secretion by activation of the parasympathetic nerves.

Defects of both diet-induced thermogenesis and cold tolerance have been reported for streptozotocin-diabetic rats. Since brown adipose tissue (BAT) is a major effector of both diet- and cold-induced thermogenesis in the rat, the possible cause of these defects was investigated by comparing BAT metabolism under basal conditions and during activation by nerve stimulation, norepinephrine (NE), or octanoate addition in both streptozotocin-diabetic rats and in controls. The following metabolic indices were measured in rat interscapular BAT (IBAT): 1) tissue composition, 2) heat production rate as measured by direct microcalorimetry, 3) redox state of flavoproteins linked to the acyl-coenzyme A dehydrogenase pathway as measured by reflection spectrometry, 4) redox state of NAD(P) as measured by surface-emitted fluorescence, and 5) fatty acid activation and beta-oxidation activities in IBAT homogenate. In streptozotocin-diabetic rats, IBAT was atrophied (DNA content unmodified, protein and lipid content decreased). The basal and NE-stimulated total heat production rates showed a 75% and 56% decrease, respectively. The specific activity of fatty acid beta-oxidation as measured by flavoprotein redox state or enzymatically was decreased by 52% and 59%, respectively. The basal redox level of NAD(P) was about 3 times higher than in the controls and NE stimulation resulted in oxidation in contrast to the reduction observed in control tissues. These results show that the metabolic capacity of IBAT from streptozotocin-diabetic rats is decreased and further suggest that the reduced capacity for beta-oxidation contributes significantly to the metabolic alteration.

The metabolic capacity of interscapular brown adipose tissue of hypoinsulinemic (diabetic) rats is decreased and a reduced &oxidative capacity contributes to this metabolic alteration. It was thus of interest to compare, in diabetic and in chronically (8 days) insulin-infused rats, the &oxidative capacity and indices of the thermogenic state (GDP-binding and 32000 A4, protein) in this tissue. Mitochondrial GDP-binding and 32000 IV, protein were both decreased in diabetic rats compared to appropriate controls and markedly increased as was also the fl-oxidative capacity in hyperinsulinemic rats.

The anatomical sites and the rates of extrapancreatic secretion of glucagon and of glucagonlike immunoreactivity (GLI) were assessed in dogs 2 h after pancreatectomy by catheterization of the gastrosplenic and mesenteric veins.Glucagon release from the gastrosplenic area approximated one-fourth that of a normal pancreas and rose from 0.25 to 1.0 ng/kg per min during arginine stimulation. Intestinal glucagon secretion was small and did not respond to arginine, suggesting that the stomach is the only important extrapancreatic source of glucagon.Glucagon concentrations attained by gastrosplenic secretion were in close proportion to those obtained during the administration of exogenous glucagon, indicating similar clearance rates of extrapancreatic and pancreatic glucagon, approximating 10 ml/kg per min.GLI secretion (0.3 ng eq/kg per min) was limited to the intestinal area and was transiently stimulated by arginine and exogenous glucagon. Base-line GLI clearance approximated 1 ml/kg per min. No insulin secretion could be detected. Gastrointestinal glucose uptake rose from 0.56 to 2.2 mg/kg per min after glucagon administration suggesting that as much as 10% of total glucose production can be taken up by the gastrointestinal tract.

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