- Email: [email protected]
Human pancreatic β-cells have potential to regenerate in vivo
78
Letter to the Editor dorsal pancreas within one family, Gastrointest. Endosc. 42 (1995) 485 /487.
Wolfgang J. Schnedl, Rainer W. Lipp Department of Internal Medicine,
Karl-Franzens University, Auenbruggerplatz 15, A-8036 Graz, Austria E-mail address: [email protected] doi: 10.1016/S0168-8227(03)00068-8
Reply to the Letter to the Editor Human pancreatic regenerate in vivo
b-cells
have
potential
to
To the Editor, Scbnedl and Lipp have raised a relevant question ‘Can Human pancreatic beta cells regenerate in vivo?’ in response to our review on ‘Models of Pancreatic Regeneration in Diabetes’ [1]. Although pancreatic regeneration after partial resection or pancreatic injury has been demonstrated in animal models, whether regeneration occurs in human pancreas is controversial. Studies by Tisotos et al. revealed that human pancreas does not regenerate after partial anatomical (50%) resection [2]. However Schelgel et al. confirmed pancreatic regeneration in human after corporocaudal splenopancreatectomy as evidenced by CT scan images showing a normal body and tail of the regenerated pancreas one year after the initial surgery. The patient remained asymptomatic, without diabetes and with no dietary restrictions [3]. The presence of islets of langerhans located within the epithelium of human pancreatic duct has been reported earlier, indicating origin of the islet from pancreatic duct [4]. Moreover extrainsular beta cells have also been observed in association with ductules in adult human pancreas [5]. Recently islet generation from human pancreatic duct cells in vitro has been reported [6]. All these studies provide sufficient documentation for the potential of regeneration in human pancreatic beta cells. Schnedl’s query about the absence of regeneration in a Caucasian family with agenesis of the dorsal pancreas and marked defects in hepatic
glycogen metabolism may reflect a defect in hepatocyte nuclear factors (HNF 1a and HNF 4a). It appears that the mother in this case may be homozygous null mutant for HNF 4a, inhibiting pancreatic regeneration as HNF 4a and la control a common genetic program in beta cells and are required for correcting the function of differentiated beta cells [7]. The non-diabetic sons in this family may be heterozygous mutants for one of the genes and hence show a less pronounced defect in insulin secretion. Indeed it remains to be seen whether pancreatic regeneration could be triggered in the genetically predisposed diabetic patients Logically, such individuals will have lesser capacity for pancreatic regeneration due to their genetic makeup.
References [1] M.V. Risbud, R.R. Bhonde, Modls of pancreatic regeneration in diabetes, Diabetes Res. Clin. Pract. 58 (2002) 155 / 165. [2] G.G. Tisotos, M.K. Barry, C.D. Johnson, M.G. San, Pancreas regeneration after resection: does it occur in human?, Pancreas 19 (1999) 310 /313. [3] R.D. Schelgel, O. Tiscornia, E. de Vedia y Mitre, et al., Is there pancreatic regeneration? Morphological and functional certification after a corporocaudal splenopancreatectomy, Acta Gastoenterol Latinoam 30 (2000) 107 /113. [4] F.J. Swartz, P.H. Carstens, An islet of langerhans located within the epithelium of a human pancreatic duct, Histol. Histopathol. 1 (1986) 111 /117. [5] L. Bowens, D.G. Pipeleers, Extra-insular beta cells associated with ductules are frequent in adult human pancreas, Diabetologia 41 (1998) 629 /633.
Letter to the Editor [6] S. Bonner-Weir, M. Taneja, G.C. Weir, et al., In vitro cultivation of human islets from expanded ductal tissue, Proc. Natl. Acad. Sci. 97 (2000) 7999 /8004. [7] J. Ferrer, A genetic switch in pancreatic beta cells. Implications for differentiation and haploinsufficiency, Diabetes 51 (2002) 2355 /2362.
79
R.R. Bhonde National Centre for Cell Science, NCCS complex, Ganeshkhind, Pune University campus, Pune 11007, MS, India E-mail address: [email protected] doi: 10.1016/S0168-8227(03)00069-X
Letter to the Editor dorsal pancreas within one family, Gastrointest. Endosc. 42 (1995) 485 /487.
Wolfgang J. Schnedl, Rainer W. Lipp Department of Internal Medicine,
Karl-Franzens University, Auenbruggerplatz 15, A-8036 Graz, Austria E-mail address: [email protected] doi: 10.1016/S0168-8227(03)00068-8
Reply to the Letter to the Editor Human pancreatic regenerate in vivo
b-cells
have
potential
to
To the Editor, Scbnedl and Lipp have raised a relevant question ‘Can Human pancreatic beta cells regenerate in vivo?’ in response to our review on ‘Models of Pancreatic Regeneration in Diabetes’ [1]. Although pancreatic regeneration after partial resection or pancreatic injury has been demonstrated in animal models, whether regeneration occurs in human pancreas is controversial. Studies by Tisotos et al. revealed that human pancreas does not regenerate after partial anatomical (50%) resection [2]. However Schelgel et al. confirmed pancreatic regeneration in human after corporocaudal splenopancreatectomy as evidenced by CT scan images showing a normal body and tail of the regenerated pancreas one year after the initial surgery. The patient remained asymptomatic, without diabetes and with no dietary restrictions [3]. The presence of islets of langerhans located within the epithelium of human pancreatic duct has been reported earlier, indicating origin of the islet from pancreatic duct [4]. Moreover extrainsular beta cells have also been observed in association with ductules in adult human pancreas [5]. Recently islet generation from human pancreatic duct cells in vitro has been reported [6]. All these studies provide sufficient documentation for the potential of regeneration in human pancreatic beta cells. Schnedl’s query about the absence of regeneration in a Caucasian family with agenesis of the dorsal pancreas and marked defects in hepatic
glycogen metabolism may reflect a defect in hepatocyte nuclear factors (HNF 1a and HNF 4a). It appears that the mother in this case may be homozygous null mutant for HNF 4a, inhibiting pancreatic regeneration as HNF 4a and la control a common genetic program in beta cells and are required for correcting the function of differentiated beta cells [7]. The non-diabetic sons in this family may be heterozygous mutants for one of the genes and hence show a less pronounced defect in insulin secretion. Indeed it remains to be seen whether pancreatic regeneration could be triggered in the genetically predisposed diabetic patients Logically, such individuals will have lesser capacity for pancreatic regeneration due to their genetic makeup.
References [1] M.V. Risbud, R.R. Bhonde, Modls of pancreatic regeneration in diabetes, Diabetes Res. Clin. Pract. 58 (2002) 155 / 165. [2] G.G. Tisotos, M.K. Barry, C.D. Johnson, M.G. San, Pancreas regeneration after resection: does it occur in human?, Pancreas 19 (1999) 310 /313. [3] R.D. Schelgel, O. Tiscornia, E. de Vedia y Mitre, et al., Is there pancreatic regeneration? Morphological and functional certification after a corporocaudal splenopancreatectomy, Acta Gastoenterol Latinoam 30 (2000) 107 /113. [4] F.J. Swartz, P.H. Carstens, An islet of langerhans located within the epithelium of a human pancreatic duct, Histol. Histopathol. 1 (1986) 111 /117. [5] L. Bowens, D.G. Pipeleers, Extra-insular beta cells associated with ductules are frequent in adult human pancreas, Diabetologia 41 (1998) 629 /633.
Letter to the Editor [6] S. Bonner-Weir, M. Taneja, G.C. Weir, et al., In vitro cultivation of human islets from expanded ductal tissue, Proc. Natl. Acad. Sci. 97 (2000) 7999 /8004. [7] J. Ferrer, A genetic switch in pancreatic beta cells. Implications for differentiation and haploinsufficiency, Diabetes 51 (2002) 2355 /2362.
79
R.R. Bhonde National Centre for Cell Science, NCCS complex, Ganeshkhind, Pune University campus, Pune 11007, MS, India E-mail address: [email protected] doi: 10.1016/S0168-8227(03)00069-X