Preserved incretin effect after complete surgical denervation of the pancreas in young pigs

Nauck, Michael A.; Hoorn, Wolbert van den; Gubernatis, G.; Ebert, R.; Siewert, J R; Creutzfeldt, W.

doi:10.1007/bf01851954

Cited by 22 publications

(5 citation statements)

References 17 publications

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“…However, in another study, also in dogs, the incretin effect was preserved after pancreatic transplantation (62). In pigs, the incretin effect was unchanged after pancreas transplantation (63). The most likely explanation may be that both neural and endocrine mechanisms are operative.…”

Section: Discussionmentioning

confidence: 93%

Characterisation of oral and i.v. glucose handling in truncally vagotomised subjects with pyloroplasty

Plamboeck

Veedfald

Deacon

et al. 2013

European Journal of Endocrinology

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ObjectiveGlucagon-like peptide 1 (GLP1) is rapidly inactivated by dipeptidyl peptidase 4 (DPP4), but may interact with vagal neurons at its site of secretion. We investigated the role of vagal innervation for handling of oral and i.v. glucose.Design and methodsTruncally vagotomised subjects (n=16) and matched controls (n=10) underwent 50 g-oral glucose tolerance test (OGTT)±vildagliptin, a DPP4 inhibitor (DPP4i) and isoglycaemic i.v. glucose infusion (IIGI), copying the OGTT without DPP4i.ResultsIsoglycaemia was obtained with 25±2 g glucose in vagotomised subjects and 18±2 g in controls (P<0.03); thus, gastrointestinal-mediated glucose disposal (GIGD) – a measure of glucose handling (100%×(glucoseOGTT−glucoseIIGI/glucoseOGTT)) – was reduced in the vagotomised compared with the control group. Peak intact GLP1 concentrations were higher in the vagotomised group. Gastric emptying was faster in vagotomised subjects after OGTT and was unaffected by DPP4i. The early glucose-dependent insulinotropic polypeptide response was higher in vagotomised subjects. Despite this, the incretin effect was equal in both groups. DPP4i enhanced insulin secretion in controls, but had no effect in the vagotomised subjects. Controls suppressed glucagon concentrations similarly, irrespective of the route of glucose administration, whereas vagotomised subjects showed suppression only during IIGI and exhibited hyperglucagonaemia following OGTT. DPP4i further suppressed glucagon secretion in controls and tended to normalise glucagon responses in vagotomised subjects.ConclusionsGIGD is diminished, but the incretin effect is unaffected in vagotomised subjects despite higher GLP1 levels. This, together with the small effect of DPP4i, is compatible with the notion that part of the physiological effects of GLP1 involves vagal transmission.

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Section: Discussionmentioning

confidence: 93%

Characterisation of oral and i.v. glucose handling in truncally vagotomised subjects with pyloroplasty

Plamboeck

Veedfald

Deacon

et al. 2013

European Journal of Endocrinology

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“…In patients with non–insulin‐dependent (type 2) diabetes mellitus (NIDDM) a reduced or absent incretin effect has been described (Nauck et al , 2003). In addition, in those patients, increased, rather than impaired, GIP secretion was observed (Nauck et al , 1985; Vaag et al ., 1996), and the responsiveness of the endocrine pancreas to GIP was greatly reduced due to underexpression of endocrine pancreatic GIP receptors (Holst et al , 1997). This reduced responsiveness to GIP is probably an early step in the pathogenesis of type 2 diabetes (Nauck et al , 2004).…”

Section: Introductionmentioning

confidence: 99%

Glucose‐dependent insulinotropic polypeptide–producing K cells in dexamethasone‐treated rats

Koko

Todorovic

Drndarević

et al. 2008

Journal of Microscopy

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SummarySome studies indicate that diabetes mellitus exerts an influence on the gastrointestinal tract and its diffuse neuroendocrine system (DNES) in regard to cellular density and neuroendocrine content. Since there is no data about relationship between experimentally induced non-insulindependent (type 2) diabetes mellitus (NIDDM) on the gut K cells, the aim of our study was to investigate immunohistochemical, stereological and ultrastructural changes of rat K cells after 12 days of dexamethasone treatment. Twenty male Wistar rats aged 30 days were given daily intraperitoneally 2 mg kg -1 dexamethasone (group DEX, 10 rats) or saline (group C, 10 rats) for 12 days. Tissue specimens were obtained from each antrum with corpus and different parts of the small (SI) and large intestine (LI) of all animals. Immunohistochemistry was carried out using antisera against the GIP and insulin. Transmission electron microscopy was also used. Although, according to the literature data, rat K cells are present in the duodenum and jejunum and, to a lesser extent, in the ileum, in the present study we observed that those cells were abundant also in all parts of the LI. We observed generally that GIP-producing K cells were augmented in all parts of SI and decreased in the LI of DEX rats. Insulin immunoreactivity (ir) coexpressed with GIP-ir in K cells and was stronger in the SI of DEX rats as compared with C rats. We also found by electron microscopy that small intestinal K cells have features not only of GIPsecreted but also of insulin-secreted cells. We concluded that dexamethasone treatment caused proliferation of K cells in the rat SI, and simultaneously transformation of GIP-producing K cells to insulin-synthesizing cells.

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“…Therefore, the slightly decreased pancreatic polypeptide level in the animals receiving transplants is consistent with maintenance of pancreatic denervation, and increased insulin secretion after transplantation may be a sequela of this situation. Higher maximum insulin levels and slightly higher incremental responses of insulin to an intragastric glucose load have also been reported after complete surgical denervation, in comparison with the innervated state of the pancreas [18,25]. Lugagne et al showed that portal and systemic venous drainage in streptozotocin-diabetic rats resulted in similar basal hyperinsulinemia in comparison with controls [22].…”

Section: Discussionmentioning

confidence: 81%

Orthotopic pancreas transplantation with portal venous drainage in rats Surgical technique and metabolic effects

Kißler

Gepp

Schwille

1999

Research in Experimental Medicine

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Heterotopic pancreas transplantation in type I diabetic patients does not correct hyperglucagonemia, which is thought to be due to insufficiently suppressed glucagon release by the host pancreas. The diabetogenic effects of glucagon then have to be corrected by higher than normal insulin secretion from the transplant, with the attendant risk of earlier loss of islet cell function, and development of atherosclerosis. To establish whether this situation can be prevented, we investigated glucose homeostasis and blood lipids, as well as fecal fat and chymotrypsin as indicators for pancreatic exocrine function 14 weeks after orthotopic pancreas transplantation in inbred rats. The pancreas was resected before orthotopic transplantation of the donor pancreas with portal venous drainage (n=8). Laparotomized animals served as controls (n=8). Basal plasma glucagon, basal plasma insulin to glucagon molar ratio, and basal and integrated incremental responses of plasma glucose, insulin, and C-peptide after an oral glucose load (2 g/kg body weight) were similar in both groups. However, hepatic insulin clearance was slightly but significantly lower in the transplanted group (1.1+/- 0.1 vs 1.6+/-0.2; P<0.05). Basal plasma levels of free fatty acids, phospholipids, triglycerides, cholesterol, low-density lipoproteins, and high-density lipoproteins were unchanged after transplantation. Also unchanged were fecal fat and chymotrypsin levels, thus indicating preserved pancreatic exocrine function. We concluded that orthotopic pancreas transplantation with portal venous drainage achieves almost optimal metabolic control with respect to endocrine and exocrine pancreatic function as well as blood lipids. This technique could therefore be used to treat combined endocrine and exocrine insufficiency in chronic pancreatitis and thus enlarges the spectrum of indications for pancreas transplantation.

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Preserved incretin effect after complete surgical denervation of the pancreas in young pigs

Cited by 22 publications

References 17 publications

Characterisation of oral and i.v. glucose handling in truncally vagotomised subjects with pyloroplasty

Characterisation of oral and i.v. glucose handling in truncally vagotomised subjects with pyloroplasty

Glucose‐dependent insulinotropic polypeptide–producing K cells in dexamethasone‐treated rats

Orthotopic pancreas transplantation with portal venous drainage in rats Surgical technique and metabolic effects

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