Ab Steffens

Preganglionic innervation of the pancreas islet cells in the rat

The position and number of preganglionic somata innervating the insulin-secreting beta-cells of the endocrine pancreas were investigated in Wistar rats. This question was approached by comparing the innervation of the pancreas of normal rats with the innervation of the pancreas in alloxan-induced diabetic animals. The presumption was made that alloxan treatment destroys the beta-cells of the islet of Langerhans and results in a selective degeneration of the beta-cells innervation. Cell bodies of preganglionic fibers innervating the pancreas were identified by retrograde transport of horseradish peroxidase following pancreas injections. It was found that 25% of the cells innervating the pancreas in the left dorsal vagal motor nucleus, 50% of the cells in the ambiguous nucleus and 50% of the cells innervating the pancreas, that originate in segments C3-C4 of the spinal cord, fail to become labeled after alloxan treatment. The position and distribution of these cell groups are described in detail and are assumed to be involved in preganglionic beta-cell innervation. A second cell population in the ventral horn and intermediolateral column of the segments T3-L2 of the cord also was labeled in normal rats and was not affected by the alloxan treatment. These thoracic cell groups are thus considered as sympathetic preganglionic somata that maintain direct connections to the pancreas. Additional preliminary information is presented dealing with the general aspects of sympathetic and parasympathetic organization of the pancreas innervation.

Autonomic innervation of the pancreas in diabetic and non-diabetic rats. A new view on intramural sympathetic structural organization

Using histochemical and immunocytochemical methods the intramural neural tissue of the pancreas was investigated in non-diabetic and in alloxan-diabetic rats. It was demonstrated that the non-diabetic pancreas contains an average of 2.71 cells/mm3 tissue that react positive for activity of acetylcholinesterase and 2.38 cells/mm3 tissue that show monoamine oxidase activity. Both cholinergic and monoaminergic cells are found as solitary cells and in clusters of various sizes. All these cells are embedded in the exocrine tissue. Both histochemical methods revealed the presence of intra-insular fiber plexuses. Treatment with alloxan resulted in disappearance of intra-insular cholinergic and monoaminergic activity and also in a 68% reduction of the cholinergic cells and 54% of the monoaminergic cells in the diabetic pancreas. Application of immunocytochemical methods employing antibodies against norepinephrine and dopamine demonstrated the noradrenergic character of at least some of the monoaminergic cell groups. It is discussed how the present data and data from previous innervation studies provide evidence for an intramural ganglionic organization of the sympathetic innervation of the rat pancreas.

Metabolic and hormonal responses to adrenoceptor antagonists in exercising rats.

alpha- and beta-adrenoceptors play a key role in the regulation of nutrient supply to working muscles during exercise. To assess their influence in the regulation of substrate utilization, rats were studied during alpha- or beta-adrenoceptor blockade. Energy metabolism was studied by means of indirect calorimetry before, during, and after moderate swimming exercise. Blood samples were taken for the determination of nutrient and hormone concentrations. In addition, central venous blood samples were withdrawn for determination of blood gases, pH, and total hemoglobin concentration (c/Hb). alpha- and beta-adrenoceptor blockade decreased the rates of energy expenditure (EE) and fat oxidation (fat-ox) during and after swimming in comparison to swimming without adrenoceptor blockade. The oxidation of carbohydrates (CHO-ox) was increased in both cases. alpha-Blockade prevented the exercise-induced increase in blood glucose, plasma free fatty acids (FFA) were not affected, and plasma insulin, norepinephrine (NOR), epinephrine (EPI), and lactate were markedly increased. beta-adrenoceptor blockade prevented the exercise-induced increases in blood glucose and FFA. EPI increased slightly more than and NOR less than in the control experiment. The exercise-induced decrease in insulin was more pronounced after beta-blockade. alpha-Blockade caused a less pronounced decrease in venous oxygen saturation (SO2) and tension (PO2) than in the control experiment. The exercise-induced increase in carbon dioxide tension (PCO2) was almost absent. After beta-blockade, venous SO2 and PO2 decreased more and PCO2 increased more than in the control experiment. It is concluded that both alpha and beta-blockade restrict the rate of EE during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the Sympathoadrenal System in Exercise-Induced Inhibition of Insulin Secretion: Effects of Islet Transplantation

The present study was designed to investigate the mechanism leading to inhibition of insulin release during exercise. To investigate the influence of circulating epinephrine and norepinephrine, these catecholamines were infused intravenously in resting islet-transplanted and control rats. The role of neural influences on insulin release was investigated by a swimming exercise study in islet-transplanted and control rats, before and after adrenodemedullation. Streptozotocin-induced diabetic Albino Oxford rats received 5 μl islet tissue into the portal vein, resulting in return of normal basal glucose and insulin levels. Transplanted and control animals were provided with two permanent heart catheters to sample blood and to give infusions. Infusion of epinephrine and norepinephrine did not result in inhibition of plasma insulin levels. Blood glucose levels, as well as nonesterified fatty acids and insulin levels in plasma, were similar in both groups. After the infusion study, the animals were subjected to strenuous swimming. During exercise, plasma insulin levels decreased not only in controls, but also in the islet-transplanted group. Blood glucose and plasma catecholamine responses were identical in both groups. After adrenodemedullation, epinephrine was not detectable and the exercise-induced decrease of insulin was not affected. These results indicate that circulating epinephrine and norepinephrine in physiological concentrations do not cause inhibition of insulin secretion. Since the exercise-induced inhibition of insulin secretion is still present in rats with islet grafts, it seems reasonable to suggest that sympathetic neural influences are responsible for the inhibition of insulin release during exercise and that transplanted islets are sympathetically reinnervated.

Influence of peri-arterial hepatic denervation on the glycemic response to exercise in rats

Exercise is known to increase hepatic glucose production. Previous studies have suggested that the sympathetic nerves only marginally contribute to this process. This study examined whether increased catecholamine response or increased adrenoceptor sensitivity might have affected previous results showing no effect of hepatic denervation on the increased hepatic glucose production during exercise. Hepatic sympathetic denervated rats, sham-operated rats and control rats were forced to swim against a counter current for 15 minutes. Denervations and sham operations were performed 9 days prior to swimming. The results show that denervation did not affect the changes in levels of blood glucose, plasma FFA, and catecholamines before, during and after swimming. Furthermore, hepatic adrenoceptor sensitivity was not altered in denervated rats, since intravenous infusions of epinephrine (20 ng/min) and norepinephrine (50 ng/min) similarly changed blood glucose and plasma FFA levels in liver-denervated, sham-operated and control rats. Thus, the increase in blood glucose levels during intravenous infusion of epinephrine and norepinephrine in the respective groups was 1.2 +/- 0.3 and 1.0 +/- 0.3 mmol/l (liver-denervated rats), 1.6 +/- 0.4 and 0.7 +/- 0.3 mmol/l (sham-operated rats) and 1.3 +/- 0.3 and 0.8 +/- 0.3 mmol/l (control rats), respectively. After adrenodemedullation, however, the rise of glucose levels during swimming in liver-denervated and control rats was completely abolished. Thus, the glucose response to swimming with and without adrenodemullation was 0.1 +/- 0.4 and 1.7 +/- 0.4 mmol/l in liver-denervated rats (P < 0.01) and -0.2 +/- 0.4 and 2.2 +/- 0.2 mmol/l in control rats (P < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

METABOLIC AND HORMONAL RESPONSES TO ADRENOCEPTOR ANTAGONISTS IN 48-HOUR-STARVED EXERCISING RATS

The influence of 48 hours of starvation on sympathoadrenal regulation of nutrient utilization was investigated in rats. To assess the role of alpha- and beta-adrenoceptors, rats were studied during alpha- and beta-blockade. Energy metabolism was measured using indirect calorimetry before, during, and after moderate swimming exercise (approximately 60% maximal O2 consumption [VO2max]). Additionally, blood samples were taken for determination of nutrient and hormone concentrations. In 48-hour-starved rats, under baseline conditions, there was a reduction in energy expenditure (EE) accompanied by a shift toward fat oxidation (fat-ox) in comparison to fed rats. Exercise-induced responses in EE, fat-ox, and carbohydrate oxidation (CHO-ox) did not differ from those in fed rats. In starved rats, a stronger response to exercise of the sympathoadrenal system was observed. In comparison to control 48-hour-starved rats, blockade of alpha- and beta-adrenoceptors led to a reduction in the exercise-induced increase in EE and fat-ox. The rate of CHO-ox was slightly reduced after blockade of either adrenoceptor type. Alpha-blockade prevented the exercise-induced increase in blood glucose. Plasma free fatty acid (FFA) was not affected. Blood lactate, plasma insulin, norepinephrine (NOR), and epinephrine (EPI) were increased after alpha-blockade. Due to beta-blockade, exercise-induced increases in glucose and FFA were prevented. Blood glucose even declined below the baseline value. EPI showed an exaggerated increase, and NOR showed a smaller increase. Results obtained in starved rats support the idea that alpha-adrenoceptor blockade-induced changes in energy metabolism are the result of a diminished oxygen supply due to diminished circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of peripheral glucagon concentrations in cyclic, pregnant, and lactating rats

In the rat, peripheral glucagon concentrations were studied throughout pregnancy and lactation. Basal glucose concentrations were decreased during late pregnancy and during lactation, but basal glucagon concentrations were not affected. Infusion of glucose (7.4 mg/min) caused an elevation of the glucose concentrations, which became lower in the course of lactation, and a suppression of the glucagon concentrations which was the same throughout pregnancy and lactation. Ingestion of 336 mg of glucose or 1 g of rat chow throughout pregnancy and lactation induced a transient increase of the glucose concentrations and a biphasic glucagon response: following a short-lasting elevation, the glucagon concentrations became suppressed. The glucagon responses to these tests did not change during pregnancy and lactation. It is concluded that the regulation of the peripheral glucagon concentration is not affected by pregnancy or lactation, and that the response of the glucagon concentration to a metabolic challenge varies with the kind of test (oral or intravenous) used.