Summary
Administration of synthetic human corticotropin-releasing factor (hCRF, 2 µg/kg body weight) during simultaneous application of the opioid antagonist naloxone (1.6 mg i.v. bolus, followed by an infusion at a rate of 1.2 mg/h) produced a significant increase in plasma C-peptide levels of six male Type 2 diabetic patients which even exceeded the postprandial values. This stimulatory effect of hCRF/naloxone on plasma C-peptide was less pronounced in six healthy men. hCRF alone did not provoke any reaction of plasma C-peptide in either group.
The possibility of a paracrine, CRF-dependent mechanism in pancreatic islets which somehow involves inhibitory opioid receptors is preferentially discussed. Such a mechanism may underlie the stimulatory action of hCRF/naloxone on B cells and would explain the absent reaction of peripheral venous plasma C-peptide to hCRF alone as well as the amplifying effect of simultaneous opioid receptor blockade.
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Abbreviations
- ACTH:
-
adrenocorticotropic hormone
- C-peptide:
-
connecting-peptide
- CRF:
-
corticotropin-releasing factor
- hCRF:
-
human CRF
- oCRF:
-
ovine CRF
- min:
-
minutes
- S.D.:
-
standard deviation
- S.E.M.:
-
standard error of the mean
References
Atkinson RL (1982) Naloxone decrease food intake in obese humans. J Clin Endocrinol Metab 55:196–198
Bruni JF, Watkins WB, Yen SSC (1979) β-Endorphin in the human pancreas. J Clin Endocrinol Metab 49:649–651
Del Pozo E, Graffenried B von, Brownell J, Derrer F, Marbach P (1980) Endocrine effect of a methionine-enkephalin derivative (FK 33-824) in man. Horm Res 13:90–97
Dubois M, Pickar D, Cohen MR, Roth YF, Macnamara T, Bunney WE (1981) Surgical stress in humans is accompanied by an increase in plasma beta-endorphin immunoreactivity. Life Sci 29:1249–1254
Ehrenreich H, Goebel F-D (1986) The role of opioids in the endocrine function of the pancreas. Diabetes Res 3:59–66
Ehrenreich H, Kolmar C, Müller OA, Goebel F-D (1987) Potentiation of the hCRF-induced release of ACTH in man by an opioid antagonist. Klin Wochenschr 65:453–457
Feldman M, Kiser RS, Unger RH, Li CH (1983) β-Endorphin and the endocrine pancreas: Studies in healthy and diabetic human beings. N Engl J Med 308:349–353
Guillemin R, Vargo T, Rossier J, Minick S, Ling N, Rivier C, Vale W, Bloom F (1977) β-Endorphin and adrenocorticotropin are secreted concomitantly by the pituitary gland. Science 197:1367–1369
Karam JH, Salber PR, Forsham PH (1983) Pancreatic hormones and diabetes mellitus. In: Greenspan FS, Forsham PH (eds) Basic and clinical endocrinology. Lange Medical Publications, Los Altos, California, pp 500–545
Lytras N, Grossman A, Rees LH, Schally AV, Bloom SR, Besser GM (1984) Corticotropin releasing factor: Effects on circulating gut and pancreatic peptides in man. Clin Endocrinol 20:725–729
Nakao K, Nakai Y, Jingami H, Oki S, Junichi F, Imura H (1979) Substantial rise of plasma β-endorphin levels after insulin-induced hypoglycemia in human subjects. J Clin Endocrinol Metab 49:838–841
Nieuwenhuijzen Kruseman AC, Linton EA, Lowry PJ, Rees LH, Besser GM (1982) Corticotropin-releasing factor immunoreactivity in human gastrointestinal tract. Lancet II:1245–1246
Nieuwenhuijzen Kruseman AC, Linton EA, Ackland J, Besser GM, Lowry PJ (1984) Heterogeneous immunohistochemical reactivities of oCRF-41-like material in the human hypothalamus, pituitary and gastrointestinal tract. Neuroendocrinology 38:212–216
Oppermann D, Huber I, Krause U, Beyer J (1985) Dose-dependent hormonal and biological reactions after stimulation with hCRF. Society of Endocrinology Meeting, Washington, May 1985 (Abstract)
Petrusz P, Merchenthaler J, Maderdrut JL, Vigh S, Schally AV (1983) Corticotropin-releasing factor (CRF)-like immunoreactivity in the vertebrate endocrine pancreas. Proc Natl Acad Sci USA 80:1721–1725
Reid RL, Yen SSC (1981) β-Endorphin stimulates the secretion of insulin and glucagon in humans. J Clin Endocrinol Metab 52:592–594
Reid RL, Sandler JA, Yen SSC (1984) β-Endorphin stimulates the secretion of insulin and glucagon in diabetes mellitus. Metabolism 33:197–199
Schulte HM, Chrousos GP, Oldfield EH, Gold PW, Cutler GB, Loriaux DL (1985) Ovine corticotropin-releasing factor administration in normal men. Pituitary and adrenal responses in the morning and evening. Hormone Res 21:69–74
Shibahara S, Morimoto Y, Futurani Y, Notake M, Takahashi H, Shimizu S, Horikawa S, Numa S (1983) Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene. EMBO J 2:775–779
Torres-Aleman K, Mason-Garcia M, Schally AV (1984) Stimulation of insulin secretion by corticotropin releasing factor (CRF) in anesthetized rats. Peptides 5:541–546
Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin. Science 213:1394–1397
Vettor R, Martini C, Manno M, Cestaro S, Federspil G, Sicolo N (1985) Effects of naloxone-induced opiate receptors blockade on insulin secretion in obesity. Horm Metabol Res 17:374–375
Watkins WB, Bruni JF, Yen SSC (1980) β-Endorphin and somatostatin in the pancreatic D cell. Localization by immunocytochemistry. J Histochem Cytochem 28:1170–1174
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Dedicated to Professor Dr. N. Zöllner on the occasion of his 65th birthday
This study was supported by the Deutsche Forschungsgemeinschaft (Go 299/3-2)
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Ehrenreich, H., Kolmar, C., Pittius, C. et al. Stimulation by hCRF of C-peptide release in type 2 diabetics during concomitant opioid receptor blockade. Klin Wochenschr 66, 175–180 (1988). https://doi.org/10.1007/BF01727787
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DOI: https://doi.org/10.1007/BF01727787