Download PDF
Horm Metab Res 2012; 44(11): 861-865
DOI: 10.1055/s-0032-1321796
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Study of the Involvement of Pancreastatin in the Physiopathology of Diabetes Mellitus Associated with Nonsecreting Pituitary Adenomas

G. Prévost
1   Department of Endocrinology, University Hospital of Rouen, France, Bois Guillaume, France
2   University of Rouen, INSERM U982, Mont Saint Aignan, France
,
F. Eas
1   Department of Endocrinology, University Hospital of Rouen, France, Bois Guillaume, France
,
C. Duparc
2   University of Rouen, INSERM U982, Mont Saint Aignan, France
,
B. Cauliez
3   Department of Hormonal Biochemistry, University Hospital of Rouen, Rouen, France
,
A. Laquérrière
4   Department of Pathology, University Hospital of Rouen, Rouen, France
,
P. Fréger
5   Department of Neurosurgery, University Hospital of Rouen, Rouen, France
,
H. Lefebvre
1   Department of Endocrinology, University Hospital of Rouen, France, Bois Guillaume, France
2   University of Rouen, INSERM U982, Mont Saint Aignan, France
,
J. M. Kuhn
1   Department of Endocrinology, University Hospital of Rouen, France, Bois Guillaume, France
2   University of Rouen, INSERM U982, Mont Saint Aignan, France
› Author Affiliations
Further Information

Publication History

received 23 January 2012

accepted 18 June 2012

Publication Date:
03 August 2012 (online)

Also available at
    Permissions and Reprints

Abstract

Pancreastatin, derived from chromogranin A, inhibits insulin and stimulates glucagon secretion in rodents. Immunohistochemistry localised pancreastatin in human pancreatic islet cells and gonadotroph pituitary cells. Nonsecreting pituitary adenomas, frequently associated with diabetes mellitus, arise quasi-constantly from gonadotroph cells. We evaluated the possible involvement of pancreastatin in the physiopathology of diabetes mellitus associated with nonsecreting pituitary adenomas. Plasma pancreastatin levels were measured by radioimmunoassay in 5 groups of subjects: 10 patients with nonsecreting pituitary adenomas associated with diabetes mellitus (group I), 10 patients with nonsecreting pituitary adenomas without diabetes (Group II), 10 patients with ACTH or GH-secreting pituitary adenomas and diabetes mellitus (Group III), 10 diabetic patients without pituitary adenomas (Group IV), and 10 healthy controls (Group V). Kidney and liver functions were normal in all of them and no patient was treated with a proton pump inhibitor. All pituitary adenomas were trans-sphenoidally removed. Immunohistochemistry against pancreastatin was performed in 5 patients of each of the 3 groups of pituitary adenomas. Plasma pancreastatin levels were not different between the different groups: 182±46 pg/ml (Group I), 195±57 pg/ml (Group II), 239±42 pg/ml (Group III), 134±31 pg/ml, (Group IV), and 122±29 pg/ml (Group V). In contrast, they were significantly (p<0.05) higher before (391±65 pg/ml) than after trans-sphenoidal surgery (149±18 pg/ml) without post-surgical change in diabetes. An immunostaining against pancreastatin was found in a majority of pituitary adenomas, associated or not with diabetes mellitus. These results argue against a role of pancreastatin in the pathogenesis of diabetes mellitus associated with nonsecreting pituitary adenomas.

Key words

pancreastatin - diabetes mellitus - nonsecreting pituitary adenomas
 

  • References

  • 1 Clayton RN, Raskauskiene D, Reulen RC, Jones PW. Mortality and morbidity in Cushing’s disease over 50 years in Stoke-on Trent, UK: audit and meta-analysis of literature. J Clin Endocrinol Metab 2011; 96: 632-642
    CrossrefPubMedSearch in Google Scholar
  • 2 Fieffe S, Morange I, Petrossians P, Chanson P, Rohmer V, Cortet C, Borson-Chazot F, Brue T, Delemer B. French Acromegaly registry . Diabetes in acromegaly, prevalence, risk factors, and evolution: data from the French Acromegaly Registry. Eur J Endocrinol 2011; 164: 877-884
    CrossrefPubMedSearch in Google Scholar
  • 3 Resmini E, Minuto F, Colao A, Ferone D. secondary diabetes associated with principal endocrinopathies: the impact of new treatment modalities. Acta Diabetol 2009; 46: 85-95
    CrossrefPubMedSearch in Google Scholar
  • 4 Passa P. Diabetes trends in Europe. Diabetes Metab 2002; 18: S3-S8
    PubMedSearch in Google Scholar
  • 5 Bonaldi C, Vernay M, Roudier C, Salanave B, Oleko A, Malon A, Castetbon K, Fagot Campagna A. A first national prevalence estimate of diagnosed and undiagnosed diabetes in France in 18- to 74-year-old individuals: the French nutrition and health survey 2006/2007. Diabet Med 2011; 28: 583-589
    CrossrefPubMedSearch in Google Scholar
  • 6 Buurman H, Saeger W. Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data. Eur J Endocrinol 2006; 154: 753-758
    CrossrefPubMedSearch in Google Scholar
  • 7 Greenman Y, Stern N. Non-functioning pituitary adenomas. Best Pract Clin Endocrinol Metab 2009; 23: 625-638
    PubMedSearch in Google Scholar
  • 8 Chanson P. Gonadotroph pituitary adenomas. Ann Endocrinol 2000; 61: 258-268
    PubMedSearch in Google Scholar
  • 9 Andersen M, Ganc-Petersen J, Jorgensen JO, Mellemkjaer S, Petersen PH, Blaabjerg O, Hagen C. Hypersecretion of the alpha-subunit in clinically non-functioning pituitary adenomas: diagnostic accuracy is improved by adding alpha-subunit/gonadotropin ratio to levels of alpha subunit. Clin Invest Med 2010; 33: E203-E212
    PubMedSearch in Google Scholar
  • 10 Samejima N, Yamada S, Takada K, Sano T, Ozawa Y, Shimizu T, Usui M, Shishiba Y. Serum alpha-subunit levels in patients with pituitary adenomas. Clin Endocrinol 2001; 54: 479-484
    CrossrefPubMedSearch in Google Scholar
  • 11 Deftos LJ, O’Connor DT, Wilson CB, Fitzgerald PA. Human pituitary tumors secret chromogranin A. J Clin Endocrinol Metab 1989; 68: 869-872
    CrossrefPubMedSearch in Google Scholar
  • 12 Huttner WB, Benedum UM. Chromogranin A and pancreastatin. Nature 1987; 325: 305
    PubMedSearch in Google Scholar
  • 13 Funakoshi S, Tamamura H, Ohta M, Yoshizawa K, Funakoshi A, Miyasaka K, Tateishi K, Tatemoto K, Nakano I, Yajima H, Fujii N. Isolation and characterization of a tumor-derived human pancreastatin-related protein. Biochem Biophys Res Commun 1989; 164: 141-148
    CrossrefPubMedSearch in Google Scholar
  • 14 Sanchez-Margalet V, Gonzalez-Yanes C. Pancreastatin inhibits insulin action in rat adipocytes. Am J Physiol Endocrinol Metab 1998; 275: 1055-1060
    PubMedSearch in Google Scholar
  • 15 Lloyd RV, Jin L, Qian X, Scheithauer BW, Young WF, Davis DH. Analysis of the chromogranin A post-translational cleavage product pancreastatin and the prohormone convertases PC2 and PC3 in normal and neoplastic human pituitaries. Am J Pathol 1995; 146: 1188-1198
    PubMedSearch in Google Scholar
  • 16 Jin L, Scheithauer BW, Young WF, Davis DH, Klee GG, Lloyd RV. Pancreastatin secretion by pituitary adenomas and regulation of chromogranin B mRNA expression. Am J Pathol 1996; 148: 2057-2066
    PubMedSearch in Google Scholar
  • 17 Efendic S, Tatemoto K, Mutt V, Quan C, Chang D, Ostenson CG. Pancreastatin and islet hormone release. Proc Natl Acad Sci USA 1987; 84: 7257-7260
    CrossrefPubMedSearch in Google Scholar
  • 18 Gonzalez-Yanes C, Sanchez-Margalet V. Pancreastatin, a chromogranin A-derived peptide, inhibits insulin-stimulated glycogen synthesis by activating GSK-3 in rat adipocytes. Biochem Biophys Res Commun 2001; 89: 282-287
    PubMedSearch in Google Scholar
  • 19 Tatemoto K, Efendic S, Mutt V, Makk G, Feistner GJ, Barchas JD. Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature 1986; 324: 476-478
    CrossrefPubMedSearch in Google Scholar
  • 20 Sanchez-Margalet V, Gonzales-Yanes C, Najib S, Santos-Alvarez J. Metabolic effects and mechanism of action of the chromogranin A-derived peptide pancreastatin. Regul Peptides 2010; 161: 8-14
    CrossrefPubMedSearch in Google Scholar
  • 21 Ahren B, Lindskog S, Tatemoto K, Efendic S. Pancreastatin inhibits insulin secretion and stimulates glucagon secretion in mice. Diabetes 1988; 37: 281-285
    CrossrefPubMedSearch in Google Scholar
  • 22 Gonzales-Yanes C, Sanchez-Margalet V. Pancreastatin modulates insulin signaling in rat adipocytes: mechanism of cross-talk. Diabetes 2000; 49: 1288-1294
    CrossrefPubMedSearch in Google Scholar
  • 23 Gayen JR, Saberi M, Schenk S, Biswas N, Vaingankar SM, Cheung WW, Najjar SM, O’Connor DT, Bandyopadhyay G, Mahata SK. A novel pathway of insulin sensitivity in chromogranin A null mice, a crucial role for pancreastatin in glucose homeostasis. J Biol Chem 2009; 284: 28498-28509
    CrossrefPubMedSearch in Google Scholar
  • 24 O’Connor DT, Cadman PE, Smiley C, Salem RM, Rao F, Smith J, Funk SD, Mahata SK, Wen G, Taupenot L, Gonzalez-Yanes C, Harper KL, Henry RR, Sanchez-Margalet V. Pancreastatin: multiple actions on human intermediary metabolism in vivo, variation in disease, and naturally occurring functional genetic polymorphism. J Clin Endocrinol Metab 2005; 90: 5414-5425
    CrossrefPubMedSearch in Google Scholar
  • 25 Funakoshi A, Tateishi K, Shinozaki H, Matsumoto M, Wakasugi H. Elevated plasma levels of pancreastatin (PST) in patients with non-insulin-dependent diabetes mellitus (NIDDM). Regul Peptides 1990; 30: 159-164
    CrossrefPubMedSearch in Google Scholar
  • 26 Sanchez-Margalet V, Lobon JA, Gonzales A, Escobar-Jimenez F, Goberna R. Increased plasma pancreastatin-like levels in gestational diabetes. Diabetes Care 1998; 21: 1951-1954
    CrossrefPubMedSearch in Google Scholar
  • 27 Heaney AP, Curry WJ, Pogue KM, Armstrong VL, Mirakhur M, Sheridan B, Johnston CF, Buchanan KD, Atkinson AB. Immunohistochemical evaluation of the post-translational processing of chromogranin A in human pituitary adenomas. Pituitary 2000; 3: 67-75
    CrossrefPubMedSearch in Google Scholar
  • 28 Jin L, Kulig E, Qian X, Scheithauer BW, Young WF, Davis DH, Seidah NG, Chretien M, Llyod RV. Distribution and regulation of proconvertases PC1 and PC2 in human pituitary adenomas. Pituitary 1999; 1: 187-195
    CrossrefPubMedSearch in Google Scholar
  • 29 Gussi IL, Young J, Baudin E, Bidart JM, Chanson P. Chromogranin A as serum marker of pituitary adenomas. Clin Endocrinol 2003; 59: 644-648
    CrossrefPubMedSearch in Google Scholar
  • 30 Tadeishi K, Funakoshi A, Wakasugi H, Iguchi H, Shinozaki H, Abe M, Funakoshi S, Tamamura H, Yajima H, Matsuoka Y. Plasma pancreastatin-like immunoreactivity in various diseases. J Clin Endocrinol Metab 1989; 69: 1305-1308
    CrossrefPubMedSearch in Google Scholar
  • 31 Tadeishi K, Miyasaka K, Shinozaki H, Funakoshi S, Matsuoka Y, Funakoshi A. Pancreastatin like immunoreactivity in urine. J Clin Endocrinol Metab 1990; 71: 842-845
    CrossrefPubMedSearch in Google Scholar
  • 32 Pornet C, Bourdel-Marchasson I, Lecomte P, Eschwège E, Romon I, Fosse S, Assogba F, Roudier C, Fagot-Campagna A. ENTRED Scientific Committee . Diabetes Metab 2011; 37: 152-161
    CrossrefPubMedSearch in Google Scholar