Insulin response to a short stress period

Psychoneuroendocrinology,Vol. 14, No. 3, pp. 241-244, 1989

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INSULIN RESPONSE TO A SHORT STRESS PERIOD MIGUEL A. ALVAREZ,LIHA PORTILLA,ROBERTOGONZALEZand ENRIQUEEZCURRA National Institute of Endocrinology,Havana, Cuba (Received 20 October 1987; in final form 22 November 1988)

SUMMARY In 24 healthy volunteers (seven women, 17 men; mean age 23+5 years), we studied the insulin response to a short stress period of 30 rain, induced by cognitive conflict under social pressure. Insulin, growth hormone (GH), blood glucose and blood pressure (BP) determinations were performed before and after the stress period. There was a significant increase in insulin levels following the stress period (10=0.02,paired t-tes0. A multiple stepwise regression analysis, with insulin difference as the dependent variable and initial GH and blood sugar levels, their increments and body mass index as predictors, showed that insulin variation was independent of any of the predictors. We discuss the influence of autonomic innervation on insulin secretion and the possible change in insulin sensitivity during stress.

INTRODUCTION THE STUDY of psychoneuroendocrine and stress factors in the regulation of carbohydrate metabolism has produced conflicting results (Chase & Jackson, 1981; Paletta et al., 1981; Rihmer & Arato, 1982; Barglow et al., 1984). Empirical clinical evidence for the relation between emotional factors and difficulties in metabolic control in type H diabetes mellitus (DM) contrast with the poor formation available about the psychoendocrine pathways linking stressful stimulation and insulin release (Vigas et al., 1972; 1973). Adrenaline release under stress conditions (Frankenhaeuser, 1980) should have an inhibitory effect on insulin secretion, leading to hyperglycemia (Surwit & Feinglos, 1984), but the issue is far from being well understood. Real-life stress studies present special methodological difficulties because of the possible effect of spurious variables (Forsman, 1983; Dimsdale, 1984). The use of experimental models provides the proper standardization for the analysis of complex psychoneuroendocrine processes, such as the influence of neural factors on insulin secretion. L o y et al. (1988) designed a stress model of 30 min duration, based on a cognitive conflict under social pressure, which produces a significant and consistent rise in blood pressure (BP) and subjective stress reactions in healthy volunteers. Using Loy's model, in the present study we have explored the insulin response to this kind of stressful stimulation in healthy volunteers. Our objective was to identify psychoendocrine response patterns for further comparison with those of type II diabetics in a research program aimed at elucidating the influence of psychosocial stress factors affecting carbohydrate metabolism. Correspondenceto be addressed to: CDr.Mignel A. Alvarez, Department of Psychology, National Institute of Endocrinology, Zapata & D, Havana 4, CUBA. 241

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SUBJECTS AND METHODS We studied 24 healthy volunteers with no endocrine or systemic disease, 17 men and seven women with mean age 23+5 years. In the fasting state they reported to the clinic at 0730h. They were asked to rest, sitting for 10 min, and then a 7 ml blood sample was taken from an antecubital vein for the basal insulin, GH, and blood sugar determinations. Blood pressure was then measured with a random zero sphygmomanometer, the mean of three determinations being used. Subjects remained in the room with three investigators. One gave them tasks to execute, and the other two criticized the subject's performance, regardless of its true merits, to create a climate of distress (Frankenhaeuser, 1986). Tasks of mental calculations were assigned for 10 min, after which the subjects were given the concentrated attention test of Tolouse-Pieron (Szkely, 1966; Alvarez et al., 1983) over 5 min. This is a perceptual motor skill test, for investigating concentration/attention, used in the clinical diagnoses of organic brain disturbances. The test procedure consists of giving the subject a sheet of paper with 460 symbols in eight slightly different variations, and instructing the subject to make a mark in the symbols previously assigned by the examiner as fast as he or she carl.

Following this task, the subjects were given 10 jumbled sentences and were asked to build the sentences correctly, while they were simultaneously requested to mention words of certain number of letters over 10 min. They concluded with a specially designed task of manual skills, in which pins had to be inserted into small holes. The stressful stimulation ended after 30 min. While the subjects were still seated the second blood sample was taken and BP again was determined. Blood samples were centrifuged, and the plasma was stored at -20* C. Insulin and growth hormone (GH) determinations were performed by a double antibody radioimmunoassay method (Hales & Randle, 1963), with an inter-assay coefficient of variations of 4.1%. Blood sugar was determined by the glucose hexokinase method (Schmidt, 1961), with a coefficient of variation of 2.4%. Both samples from each subject were measured in the same assay in order to minimize inter-assay variation. Body mass index (BMI) (Keys, 1972) was calculated for each subject. RESULTS Table I shows the initial and final values o f BP. A significant increase was o b s e r v e d (p<0.01, p a i r e d t - t e s t ) , i n d i c a t i n g the p s y c h o p h y s i o l o g i c a l a r o u s a l o c c u r r i n g d u r i n g the experiment. Table II shows the initial and final values o f insulin and blood sugar. Insulin values had the e x p e c t e d l o g - n o r m a l distribution and s h o w e d a significant increase during the stress period (p<0.025, paired t-test). Subjects 7 and 10, who developed considerable increase in insulin levels, were both men, 24 and 22 years old, whose B M I were 23.3 and 21, respectively, thus lacking any unusual characteristics c o m p a r e d to the rest o f the group. No significant trend o f values in either direction occurred for G H or b l o o d sugar. To determine if the significant rise in insulin could be related to the fluctuations of GH and blood sugar, we performed a stepwise multiple regression analysis, taking the insulin variations (difference score) as the d e p e n d e n t variable and the initial G H and blood sugar values, their difference scores, and B M I as predictors. None of the independent variables met the significance criterion for entering the equation, suggesting that the individual insulin variations were due to other factors.

TABLE I. BLOOD PKF~SU~ (MEAN~.SD) DURING THE STRESS ~PJOD.

Initial Diastolic Systolic *p
68.47 + 9.72 108.38 + 11.77

Final 78.71+ 8.97* 118.95 + 9.70*

INsutmREsPonsETOSaaw_ss

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TABLE II. INSULIN(~tU/ML)ANDBLOODSUGAR(MCJ%)DURINGTHE STRESSPERIOD. Insulin Subjects

1

2

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

6 36 6 19 8 7 16 9 3 22 7 7 13 9 13 9 28 4

13 25 6 18 7 1.2 74 9 11 48 5 13 18 16 25 9 29 19

7

Mean S.D.

14 11 14 13 3 11.83 9.93

6

22 8 22 15 4 17.63" 15.76

Blood Sugar 1 2

........ ........ 98 101 ........ ........ 77 ........ 95 118 67 101 107 79 64 109 127 98 ........ 68 90 76 103 84 92.63 17.49

94 87 84 88 123 70 113 119 90 66 86 87 102 75 88 79 104 83 91.15 15.37

* Significant difference between insulin 1 and 2 (p
DISCUSSION We have two results of this study: the expected rise in BP, indicating a psychophysiological arousal probably mediated by adrenalin, and an increase in insulin levels, independent of GH, blood sugar and BMI. The s y m p a t h e t i c and p a r a s y m p a t h e t i c nervous systems innervate pancreatic islets. Acetylcholine, norepinephrine and epinephrine have been shown to influence islet cells. Acetylcholine stimulates insulin release only during periods of elevated blood sugar, but catecholamines stimulate the cx-adrenergic receptors, inhibiting insulin release, and also stimulate [~-adrenergic receptors, which tend to increase insulin secretion. The hypothalamus (ventrolateral and ventromedial areas) seems to play an integrating role in the autonomic regulation of the islet (Porte & Halter, 1981). Endogenous opiate peptides acting within the autonomic nervous system also may be of importance in the modulation of insulin secretion (Benfenati et al., 1984). Another possibility is that stress could have provoked glucogenolysis and brought about an undetected rise in blood sugar between the initial and final determinations, which might have stimulated the pancreas to release insulin. Frequent blood sampling would be needed to evaluate this hypothesis. A relative insulin resistance during depression has been reported, probably associated with hypersecretion of cortisol (Rose & Sachar, 1981). Although the design of our experiment does not make possible the testing of this hypothesis, the lack of variation in blood glucose levels in

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