Cytological differentiation of asymptomatic pancreatic islet cell tumours in autopsy material

Grimelius, Lars; Hultquist, Gösta T.; Stenkvist, Björn

doi:10.1007/bf00471177

Cited by 96 publications

(43 citation statements)

References 16 publications

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“…However, in humans, similar, clearly age-dependent changes have been observed in autopsy studies [31,32] suggesting that the Butler observations are mainly due to the age difference between the groups. The hyperplasia in the Butler study led some to think of the alpha cell hyperplasia that has been observed in mice with glucagon receptor mutations and animals treated with glucagon antagonists [33,34], based on the idea that, if GLP-1 therapies inhibit glucagon secretion, they may also cause alpha cell hyperplasia.…”

Section: Dpp-4 Dipeptidyl Peptidase-4 Glp-1 Glucagon-like Peptide-1supporting

confidence: 69%

Pancreatic safety of GLP-1-based therapeutic agents: further insights from rodent studies?

Holst

2013

Diabetologia

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Abbreviations DPP-4 Dipeptidyl peptidase-4 GLP-1 Glucagon-like peptide-1In this issue of Diabetologia, Ellenbroek and colleagues present a study of the effects of the glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, on beta cell function and mass in normoglycaemic mice [1]. The mice were treated with liraglutide at 0.1 mg/kg twice daily (a high but reasonable dose) for either 1 or 6 weeks while they received either a control diet or a high fat diet. Compared with controls, liraglutide improved insulin resistance and attenuated resistance induced by high fat feeding. In the pancreas, a lower beta cell mass was observed in the liraglutide-treated group, which was associated with decreased proliferation of beta cells at 1 week. Despite this, islets isolated from treated mice showed enhanced glucose-stimulated insulin secretion. There was a similar reduction in alpha cell mass such that the alpha to beta cell ratio was preserved. In contrast, acinar cells showed a significantly higher number of proliferating cells following liraglutide treatment in both control and high fat fed mice (as measured using BrdU incorporation), and total pancreatic mass increased somewhat after 6 weeks. Duct cells did not show proliferation. There were no signs of inflammation and levels of pro-inflammatory cytokines were similar in all groups.These results are interesting in many ways. First, the reported effect on beta cell mass is consistent with the view that beta cell mass in rodents is predominantly regulated by glucose [2]. Thus, the proliferative effects of GLP-1 and GLP-1 agonists are mainly observed in hyperglycaemic animals. Bock et al [3] observed that the effect of liraglutide on beta cell mass (evaluated by stereology, the most reliable technique for morphometric analysis) in normoglycaemic rats was transient, supporting the view that glycaemic regulation overrides the effects of incretins. The lower beta cell mass observed by Ellenbroek et al is consistent with a glucose-lowering effect of GLP-1 even at basal levels [4]. The positive effects on insulin sensitivity and glucose tolerance are in line with those observed in human studies [5], although the mechanism in normoglycaemic animals is unclear. The question is whether or not GLP-1 directly affects peripheral insulin-sensitive tissues (muscle and fat); this has been reported in rodents [6], but is perhaps less likely to occur in humans [7,8], where improvements in patients with diabetes are generally thought to reflect improved metabolism and weight loss [5]. Weight loss may also play a role in the present study [1], as liraglutide treatment reduced body weight in control and high fat fed mice.A new finding in this study is that alpha cell mass was reduced similarly to beta cell mass [1]. Initially, this would appear consistent with the inhibitory effect of GLP-1 on alpha cell secretion [9]. However, the mechanism behind the inhibition is far from clear: in contrast to beta cells, it is highly controversial whether or not alpha cells express GLP-1 receptors...

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Section: Dpp-4 Dipeptidyl Peptidase-4 Glp-1 Glucagon-like Peptide-1supporting

confidence: 69%

Pancreatic safety of GLP-1-based therapeutic agents: further insights from rodent studies?

Holst

2013

Diabetologia

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“…The incidence of pancreatic neuroendocrine tumours is 17% in patients with known von Hippel-Lindau disease but only 0.5%-1.5% in unselected autopsies [13]. Unlike many cases of von Hippel-Lindau disease in which the patient commonly presents with retinal angiomas and cerebellar haemangioblastomas, in the case presented here the pancreatic neuroendocrine tumour was the first and only manifestation.…”

Section: Discussionmentioning

confidence: 70%

Von Hippel-Lindau disease presenting as pancreatic neuroendocrine tumour

et al. 1995

Vichows Archiv A Pathol Anat

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A 21-year-old woman with a family history of von Hippel-Lindau disease presented with a mass in the head of the pancreas. Light microscopic features of the tumour suggested neuroendocrine differentiation and although it displayed positive immunostaining for the antigens expected in a neuroendocrine neoplasm, S-100 staining was also present. This unusual feature prompted further evaluation by routine and post-embedding protein-A gold immunoelectron microscopy, which demonstrated the presence of neuroendocrine granules. Tumour cell DNA content was normal by flow cytometry. Although this patient exhibited no other signs of von Hippel-Lindau disease, the presence of a pancreatic tumour with neuroendocrine differentiation demonstrated that she was affected. Future surveillance and genetic counselling will be influenced by this diagnosis.

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“…The tumors show no significant gender predilection and occur at all ages, with a peak incidence between 30 and 60 years. [5][6][7] Approximately 1-2% of patients with these tumors have familial syndromes of predisposition, and the genetics of these disorders are discussed below. Figure 1 The normal endocrine pancreas.…”

Section: Epidemiologymentioning

confidence: 99%

Pancreatic endocrine tumors

Sylvia

2011

Modern Pathology

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The endocrine cells of the pancreas and their related cells throughout the gastrointestinal tract give rise to a variety of tumors that pose a diagnostic challenge. There has been progress in understanding their histogenesis, morphology, immunohistochemistry, molecular biology and classifications. This review will focus on nomenclature/terminology, classification, the role of immunohistochemistry, molecular advances, including genetic predisposition, and potential therapeutic targets to define the role of pathology in the application of prognostic and predictive markers for this disease.

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Cytological differentiation of asymptomatic pancreatic islet cell tumours in autopsy material

Cited by 96 publications

References 16 publications

Pancreatic safety of GLP-1-based therapeutic agents: further insights from rodent studies?

Pancreatic safety of GLP-1-based therapeutic agents: further insights from rodent studies?

Von Hippel-Lindau disease presenting as pancreatic neuroendocrine tumour

Pancreatic endocrine tumors

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