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Erschienen in: Journal of Gastroenterology 6/2015

01.06.2015 | Original Article—Liver, Pancreas, and Biliary Tract

Pancreatic congestion in liver cirrhosis correlates with impaired insulin secretion

verfasst von: Taira Kuroda, Masashi Hirooka, Mitsuhito Koizumi, Hironori Ochi, Yoshiko Hisano, Kenji Bando, Bunzo Matsuura, Teru Kumagi, Yoichi Hiasa

Erschienen in: Journal of Gastroenterology | Ausgabe 6/2015

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Abstract

Background

Although impaired glucose tolerance is common in cirrhosis, this condition’s pathogenesis remains undefined. This study aimed to clarify pathogenesis related to the pancreas in cirrhotic patients, and to evaluate associations between insulin secretion and pancreatic congestion due to portal hypertension.

Methods

Pancreatic perfusion parameters were analyzed by dynamic contrast-enhanced ultrasound (CE-US) in 41 patients (20 cirrhotic, 21 non-cirrhotic; age, 67.9 ± 13.3; female, 19), and prospectively compared to delta C-peptide immunoreactivity (ΔCPR). In a separate study, a retrospective chart review with human autopsy specimens was conducted, and vessels and islets of the pancreas were analyzed in 43 patients (20 cirrhotic, 23 controls; age, 71.5 ± 11.6; female, 15).

Results

In the CE-US study, the clinical characteristics indicative of portal hypertension (e.g., ascites and varices) had significantly higher incidences in the cirrhotic group than in the control group. Pancreatic drainage times were greater in the cirrhotic group (p < 0.0001), and had a significant negative correlation with ΔCPR (R = 0.42, p = 0.0069). In the histopathological study, the islets were enlarged in the cirrhotic group (p < 0.0001). However, the percentage of insulin-positive area per islet was decreased in the cirrhotic group (p < 0.0001), and had a significant negative correlation with the wall thickness of the pancreatic vein (R = 0.63, p < 0.0001).

Conclusions

Pancreatic congestion was present in cirrhotic patients. Moreover, pancreatic congestion and insulin secretion were significantly correlated. This pathogenesis could be a key factor underlying the development of hepatogenous diabetes in cirrhotic patients.
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Literatur
1.
Zurück zum Zitat Kruszynska YT, Harry DS, Bergman RN, et al. Insulin sensitivity, insulin secretion and glucose effectiveness in diabetic and non-diabetic cirrhotic patients. Diabetologia. 1993;36:121–8.PubMedCrossRef Kruszynska YT, Harry DS, Bergman RN, et al. Insulin sensitivity, insulin secretion and glucose effectiveness in diabetic and non-diabetic cirrhotic patients. Diabetologia. 1993;36:121–8.PubMedCrossRef
2.
Zurück zum Zitat Petrides AS, Schulze-Berge D, Vogt C, et al. Glucose resistance contributes to diabetes mellitus in cirrhosis. Hepatology. 1993;18:284–91.PubMedCrossRef Petrides AS, Schulze-Berge D, Vogt C, et al. Glucose resistance contributes to diabetes mellitus in cirrhosis. Hepatology. 1993;18:284–91.PubMedCrossRef
3.
Zurück zum Zitat Iversen J, Vilstrup H, Tygstrup N. Kinetics of glucose metabolism in relation to insulin concentrations in patients with alcoholic cirrhosis and in healthy persons. Gastroenterology. 1984;87:1138–43.PubMed Iversen J, Vilstrup H, Tygstrup N. Kinetics of glucose metabolism in relation to insulin concentrations in patients with alcoholic cirrhosis and in healthy persons. Gastroenterology. 1984;87:1138–43.PubMed
4.
Zurück zum Zitat Merli M, Leonetti F, Riggio O, et al. Glucose intolerance and insulin resistance in cirrhosis are normalized after liver transplantation. Hepatology. 1999;30:649–54.PubMedCrossRef Merli M, Leonetti F, Riggio O, et al. Glucose intolerance and insulin resistance in cirrhosis are normalized after liver transplantation. Hepatology. 1999;30:649–54.PubMedCrossRef
5.
Zurück zum Zitat Petrides AS, Defronzo RA. Glucose and insulin metabolism in cirrhosis. J Hepatol. 1989;8:107–14.PubMedCrossRef Petrides AS, Defronzo RA. Glucose and insulin metabolism in cirrhosis. J Hepatol. 1989;8:107–14.PubMedCrossRef
6.
Zurück zum Zitat Wu J, Lindström P, Danielsson A, et al. Insulin secretion in pancreatic islets from rats with cirrhosis. J Hepatol. 1994;21:332–9.PubMedCrossRef Wu J, Lindström P, Danielsson A, et al. Insulin secretion in pancreatic islets from rats with cirrhosis. J Hepatol. 1994;21:332–9.PubMedCrossRef
7.
Zurück zum Zitat Gomis R, Fernández-Alvarez J, Pizcutea P, et al. Impaired function of pancreatic islet from rats with portal hypertension resulting from cirrhosis and partial portal vein ligation. Hepatology. 1994;19:1257–61.PubMedCrossRef Gomis R, Fernández-Alvarez J, Pizcutea P, et al. Impaired function of pancreatic islet from rats with portal hypertension resulting from cirrhosis and partial portal vein ligation. Hepatology. 1994;19:1257–61.PubMedCrossRef
8.
Zurück zum Zitat Sakata M, Kawahara A, Kawaguchi T, et al. Decreased expression of insulin and increased expression of pancreatic transcription factor PDX-1 in islets in patients with liver cirrhosis: a comparative investigation using human autopsy specimens. J Gastroenterol. 2013;48:277–85.PubMedCrossRef Sakata M, Kawahara A, Kawaguchi T, et al. Decreased expression of insulin and increased expression of pancreatic transcription factor PDX-1 in islets in patients with liver cirrhosis: a comparative investigation using human autopsy specimens. J Gastroenterol. 2013;48:277–85.PubMedCrossRef
9.
Zurück zum Zitat Manenti A, Botticelli A, Gibertini G, et al. Experimental congestive splenomegaly: histological observations in the rat. Pathologica. 1993;85:721–4.PubMed Manenti A, Botticelli A, Gibertini G, et al. Experimental congestive splenomegaly: histological observations in the rat. Pathologica. 1993;85:721–4.PubMed
10.
Zurück zum Zitat Cavalli G, Re G, Casali AM. Red pulp arterial terminals in congestive splenomegaly: a morphometric study. Pathol Res Pract. 1984;178:590–4.PubMedCrossRef Cavalli G, Re G, Casali AM. Red pulp arterial terminals in congestive splenomegaly: a morphometric study. Pathol Res Pract. 1984;178:590–4.PubMedCrossRef
11.
Zurück zum Zitat Re G, Casali AM, Cavalli D, et al. Histometric analysis of white pulp arterial vessels in congestive splenomegaly. Appl Pathol. 1986;4:98–103.PubMed Re G, Casali AM, Cavalli D, et al. Histometric analysis of white pulp arterial vessels in congestive splenomegaly. Appl Pathol. 1986;4:98–103.PubMed
12.
Zurück zum Zitat Terayama N, Makimoto KP, Kobayashi S, et al. Pathology of the spleen in primary biliary cirrhosis: an autopsy study. Pathol Int. 1994;44:753–8.PubMedCrossRef Terayama N, Makimoto KP, Kobayashi S, et al. Pathology of the spleen in primary biliary cirrhosis: an autopsy study. Pathol Int. 1994;44:753–8.PubMedCrossRef
13.
Zurück zum Zitat Murakami T, Fujita T, Taguchi T, et al. The blood vascular bed of the human pancreas, with special reference to the insulo-acinar portal system. Scanning electron microscopy of corrosion casts. Arch Histol Cytol. 1992;55:381–95.PubMedCrossRef Murakami T, Fujita T, Taguchi T, et al. The blood vascular bed of the human pancreas, with special reference to the insulo-acinar portal system. Scanning electron microscopy of corrosion casts. Arch Histol Cytol. 1992;55:381–95.PubMedCrossRef
14.
Zurück zum Zitat Murakami T, Hitomi S, Ohtsuka A, et al. Pancreatic insulo-acinar portal systems in humans, rats, and some other mammals: scanning electron microscopy of vascular casts. Microsc Res Tech. 1997;27:478–88.CrossRef Murakami T, Hitomi S, Ohtsuka A, et al. Pancreatic insulo-acinar portal systems in humans, rats, and some other mammals: scanning electron microscopy of vascular casts. Microsc Res Tech. 1997;27:478–88.CrossRef
15.
Zurück zum Zitat VonGlahn WC, Chobot R. The histological alteration of the pancreas in chronic passive congestion. Am J Pathol. 1925;1:373–82.PubMedCentralPubMed VonGlahn WC, Chobot R. The histological alteration of the pancreas in chronic passive congestion. Am J Pathol. 1925;1:373–82.PubMedCentralPubMed
17.
Zurück zum Zitat Abràmoff MD, Magelhães PJ, Ram SJ. Image processing with ImageJ. Biophotonics Int. 2004;11:36–42. Abràmoff MD, Magelhães PJ, Ram SJ. Image processing with ImageJ. Biophotonics Int. 2004;11:36–42.
18.
Zurück zum Zitat D’Onofrio M, Zamboni G, Faccioli N, et al. Ultrasonography of the pancreas. 4. Contrast-enhanced imaging. Abdom Imaging. 2007;32:171–81.PubMedCrossRef D’Onofrio M, Zamboni G, Faccioli N, et al. Ultrasonography of the pancreas. 4. Contrast-enhanced imaging. Abdom Imaging. 2007;32:171–81.PubMedCrossRef
19.
Zurück zum Zitat Johnson-Neitman JL, O’Brien RT, Wallace JD. Quantitative perfusion analysis of the pancreas and duodenum in healthy dogs by use of contrast-enhanced ultrasonography. Am J Vet Res. 2012;73:385–92.PubMedCrossRef Johnson-Neitman JL, O’Brien RT, Wallace JD. Quantitative perfusion analysis of the pancreas and duodenum in healthy dogs by use of contrast-enhanced ultrasonography. Am J Vet Res. 2012;73:385–92.PubMedCrossRef
20.
Zurück zum Zitat Kersting S, Konopke R, Kersting F, et al. Quantitative perfusion analysis of transabdominal contrast-enhanced ultrasonography of pancreatic masses and carcinomas. Gastroenterology. 2009;137:1903–11.PubMedCrossRef Kersting S, Konopke R, Kersting F, et al. Quantitative perfusion analysis of transabdominal contrast-enhanced ultrasonography of pancreatic masses and carcinomas. Gastroenterology. 2009;137:1903–11.PubMedCrossRef
21.
Zurück zum Zitat Ripollés T, Martínez MJ, López E, et al. Contrast-enhanced ultrasound in the staging of acute pancreatitis. Eur Radiol. 2010;20:2518–23.PubMedCrossRef Ripollés T, Martínez MJ, López E, et al. Contrast-enhanced ultrasound in the staging of acute pancreatitis. Eur Radiol. 2010;20:2518–23.PubMedCrossRef
22.
Zurück zum Zitat Li T, Ni JY, Qi YW, et al. Splenic vasculopathy in portal hypertension patients. World J Gastroenterol. 2006;12:2737–41.PubMedCentralPubMed Li T, Ni JY, Qi YW, et al. Splenic vasculopathy in portal hypertension patients. World J Gastroenterol. 2006;12:2737–41.PubMedCentralPubMed
23.
Zurück zum Zitat Yang Z, Zhang L, Li D, et al. Pathological morphology alteration of the splanchnic vascular wall in portal hypertensive patients. Chin Med J. 2002;115:559–62.PubMed Yang Z, Zhang L, Li D, et al. Pathological morphology alteration of the splanchnic vascular wall in portal hypertensive patients. Chin Med J. 2002;115:559–62.PubMed
24.
Zurück zum Zitat Resch M, Wiest R, Moleda L, et al. Alterations in mechanical properties of mesenteric resistance arteries in experimental portal hypertension. Am J Physiol Gastrointest Liver Physiol. 2009;297:G849–57.PubMedCrossRef Resch M, Wiest R, Moleda L, et al. Alterations in mechanical properties of mesenteric resistance arteries in experimental portal hypertension. Am J Physiol Gastrointest Liver Physiol. 2009;297:G849–57.PubMedCrossRef
25.
Zurück zum Zitat Lamps LW, Carson K, Bradley AL, et al. Pulmonary vascular morphological changes in cirrhotic patients undergoing liver transplantation. Liver Transpl Surg. 1999;5:57–64.PubMedCrossRef Lamps LW, Carson K, Bradley AL, et al. Pulmonary vascular morphological changes in cirrhotic patients undergoing liver transplantation. Liver Transpl Surg. 1999;5:57–64.PubMedCrossRef
26.
Zurück zum Zitat Ishikawa T, Shiratsuki S, Matsuda T, et al. Occlusion of portosystemic shunts improves hyperinsulinemia due to insulin resistance in cirrhotic patients with portal hypertension. J Gastroenterol 2013 (in press). Ishikawa T, Shiratsuki S, Matsuda T, et al. Occlusion of portosystemic shunts improves hyperinsulinemia due to insulin resistance in cirrhotic patients with portal hypertension. J Gastroenterol 2013 (in press).
27.
Zurück zum Zitat Tanabe N, Ishii M, Sato Y, Akahane T, et al. Effects of collateral vessel occlusion on oral glucose tolerance test in liver cirrhosis. Dig Dis Sci. 2000;45:581–6.PubMedCrossRef Tanabe N, Ishii M, Sato Y, Akahane T, et al. Effects of collateral vessel occlusion on oral glucose tolerance test in liver cirrhosis. Dig Dis Sci. 2000;45:581–6.PubMedCrossRef
28.
Zurück zum Zitat Hirota S, Matsumoto M, Tomita M, et al. Retrograde transvenous obliteration of gastric varices. Radiology. 1999;211:349–56.PubMedCrossRef Hirota S, Matsumoto M, Tomita M, et al. Retrograde transvenous obliteration of gastric varices. Radiology. 1999;211:349–56.PubMedCrossRef
29.
Zurück zum Zitat Akahane T, Iwasaki T, Kobayashi N, et al. Changes in liver function parameters after occlusion of gastrorenal shunts with balloon-occluded retrograde transvenous obliteration. Am J Gastroenterol. 1997;92:1026–30.PubMed Akahane T, Iwasaki T, Kobayashi N, et al. Changes in liver function parameters after occlusion of gastrorenal shunts with balloon-occluded retrograde transvenous obliteration. Am J Gastroenterol. 1997;92:1026–30.PubMed
30.
Zurück zum Zitat Narita R, Abe S, Kihara Y, et al. Insulin resistance and insulin secretion in chronic hepatitis C virus infection. J Hepatol. 2004;41:132–8.PubMedCrossRef Narita R, Abe S, Kihara Y, et al. Insulin resistance and insulin secretion in chronic hepatitis C virus infection. J Hepatol. 2004;41:132–8.PubMedCrossRef
31.
Zurück zum Zitat Brüning JC, Michael MD, Winnay JN, et al. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell. 1998;2:559–69.PubMedCrossRef Brüning JC, Michael MD, Winnay JN, et al. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell. 1998;2:559–69.PubMedCrossRef
32.
Zurück zum Zitat Imai J, Katagiri H, Yamada T, et al. Regulation of pancreatic β-cell mass by neuronal signals from the liver. Science. 2008;322:1250–4.PubMedCrossRef Imai J, Katagiri H, Yamada T, et al. Regulation of pancreatic β-cell mass by neuronal signals from the liver. Science. 2008;322:1250–4.PubMedCrossRef
33.
Zurück zum Zitat Konrad T, Zeuzem S, Toffolo G, et al. Severity of HCV-induced liver damage alters glucose homeostasis in noncirrhotic patients with chronic HCV infection. Digestion. 2000;62:52–9.PubMedCrossRef Konrad T, Zeuzem S, Toffolo G, et al. Severity of HCV-induced liver damage alters glucose homeostasis in noncirrhotic patients with chronic HCV infection. Digestion. 2000;62:52–9.PubMedCrossRef
34.
Zurück zum Zitat Quigley EM, Abu-Shanab A. Small intestinal bacterial overgrowth. Infect Dis Clin North Am. 2010;24:943–59.PubMedCrossRef Quigley EM, Abu-Shanab A. Small intestinal bacterial overgrowth. Infect Dis Clin North Am. 2010;24:943–59.PubMedCrossRef
35.
Zurück zum Zitat Ouwehand A, Isolauri E, Salminen S. The role of the intestinal microflora for the development of the immune system in early childhood. Eur J Nutr. 2002;41:132–7.CrossRef Ouwehand A, Isolauri E, Salminen S. The role of the intestinal microflora for the development of the immune system in early childhood. Eur J Nutr. 2002;41:132–7.CrossRef
36.
Zurück zum Zitat Bellot P, Francés R, Such J. Pathological bacterial translocation in cirrhosis: pathophysiology, diagnosis and clinical implications. Liver Int. 2013;33:31–9.PubMedCrossRef Bellot P, Francés R, Such J. Pathological bacterial translocation in cirrhosis: pathophysiology, diagnosis and clinical implications. Liver Int. 2013;33:31–9.PubMedCrossRef
37.
Zurück zum Zitat Collins BS, Lin HC. Chronic abdominal pain in children is associated with high prevalence of abnormal microbial fermentation. Dig Dis Sci. 2010;55:124–30.PubMedCrossRef Collins BS, Lin HC. Chronic abdominal pain in children is associated with high prevalence of abnormal microbial fermentation. Dig Dis Sci. 2010;55:124–30.PubMedCrossRef
38.
Zurück zum Zitat Sherwin RS, Fisher M, Bessoff J, et al. Hyperglucagonemia in cirrhosis: altered secretion and sensitivity to glucagon. Gastroenterology. 1978;74:1244–8. Sherwin RS, Fisher M, Bessoff J, et al. Hyperglucagonemia in cirrhosis: altered secretion and sensitivity to glucagon. Gastroenterology. 1978;74:1244–8.
Metadaten
Titel
Pancreatic congestion in liver cirrhosis correlates with impaired insulin secretion
verfasst von
Taira Kuroda
Masashi Hirooka
Mitsuhito Koizumi
Hironori Ochi
Yoshiko Hisano
Kenji Bando
Bunzo Matsuura
Teru Kumagi
Yoichi Hiasa
Publikationsdatum
01.06.2015
Verlag
Springer Japan
Erschienen in
Journal of Gastroenterology / Ausgabe 6/2015
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-014-1001-8

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