Glucagon-like peptide-1 (GLP-1) receptors are not overexpressed in pancreatic islets from patients with severe hyperinsulinaemic hypoglycaemia following gastric bypass

Reubi, Jean Claude; Perren, Aurel; Rehmann, Ruth; Waser, Beatrice; Christ, Emanuel; Callery, Mark P.; Goldfine, Allison B.; Patti, Mary‐Elizabeth

doi:10.1007/s00125-010-1901-y

Cited by 57 publications

(53 citation statements)

References 12 publications

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“…There are receptors for GLP1 on a-cells and on insulin-producing b-cells and somatostatin-producing d-cells (18). The number of GLP1 receptors does not seem to be increased in islets from surgical pancreatic tissue specimens (19). The GBP procedure also induces, in addition to several changes in key glucoregulatory hormones, changes in neuronal/ sympathetic activity, the latter less well documented but is reflected for instance in marked changes in vasodilation 1 month after surgery (20).…”

Section: Discussionmentioning

confidence: 91%

GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?

Abrahamsson¹,

Engström

Sundbom

et al. 2013

European Journal of Endocrinology

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Objective: The number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a K ATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia. Design: We explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms. Results: Glucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements.Conclusion: These open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.

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Section: Discussionmentioning

confidence: 91%

GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?

Abrahamsson¹,

Engström

Sundbom

et al. 2013

European Journal of Endocrinology

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“…Notably, the 2/27 cases in this series lacking GLP-1R expression demonstrated intense staining (up to 6477 dpm/mg tissue) for SSTR2, suggesting a 'flip-flop' phenomenon. In contrast, the same group (Reubi et al 2010) demonstrated normal GLP-1R expression in seven samples of pancreatic tissue from patients with PGBH (mean density 1483 dpm/ mg tissue) compared to 10 normal controls (1563 dpm/ mg tissue), and much less than that seen in six cases of benign insulinoma (mean density 8302 dpm/mg tissue). This provided the rationale for GLP-1R imaging in the localisation of insulinoma but indicates that it is less likely to be useful in the evaluation of PGBH.…”

Section: Pathophysiology Of Hypoglycaemia Syndromesmentioning

confidence: 90%

Molecular imaging in the investigation of hypoglycaemic syndromes and their management

Pattison¹,

Hicks²

2017

Endocrine-Related Cancer

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There has been recent progress in molecular imaging using a variety of cellular targets for the investigation of adult non-diabetic hypoglycaemic syndromes and its integration into patient management. These targets include peptide receptors (somatostatin receptors (SSTRs) and glucagon-like peptide-1 receptor (GLP-1R)) the amine precursor uptake and decarboxylation system utilising the diphydroxyphenylaline (DOPA) analogue 6-[ 18 F]-l-fluoro-l-3,4-dihydroxyphenylalanine ( 18 F-FDOPA), and glycolytic metabolism with 2-[ 18 F]fluoro-2-deoxy-d-glucose (FDG). Accurate preoperative localisation and staging is critical to enable directed surgical excision or enucleation with minimal morbidity and preservation of residual pancreatic function. Benign insulinoma has near ubiquitous dense GLP-1R expression enabling accurate localisation with radiolabelled-exendin-4 compounds (e.g. 68 Ga-NOTA-exendin-4 PET/CT), whilst the rarer and more difficult to manage metastatic insulinoma typically express SSTR and is preferably imaged with radiolabelled-SSTR analogues such as 68 Ga-DOTA-octreotate (DOTATATE) PET/CT for staging and assessment of suitability for peptide receptor radionuclide therapy (PRRT). Similar to other metastatic neuroendocrine tumours, FDG PET/CT is used in the setting of highergrade metastatic insulinoma to provide important prognostic information that can guide treatment and determine suitability for PRRT. Interestingly, these three tracers appear to represent a spectrum of differentiation, which we conceptually describe as the 'tripleflop' phenomenon, with GLP-1R > SSTR > FDG in benign insulinoma and the opposite in higher-grade disease. This paper will review the clinical syndromes of adult hypoglycaemia (including a practical overview of the differential diagnoses to be considered), comparison of techniques for insulinoma localisation with emphasis on molecular imaging before discussing its implications for management of metastatic insulinoma.

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“…Attention has been mostly paid to the tenfold rise in glucagon-like peptide-1 (GLP-1) post-GBP and the subsequent steep rise in insulin and quick fall in glucose. Reports of the number of islets in the post-GBP patient's pancreas are conflicting (6,8,9), and no increase in the number of GLP-1 receptors has been observed (10). The rise in GLP-1 is higher in post-GBP patients with hyperinsulinemic hypoglycemia with neuroglucopenia (4,11), and experimental and short time blockade of the GLP-1 receptor markedly decreases insulin secretion and corrects postprandial hypoglycemia (12).…”

Section: Introductionmentioning

confidence: 99%

Hypoglycemia in everyday life after gastric bypass and duodenal switch

Abrahamsson

Engström

Sundbom

et al. 2015

European Journal of Endocrinology

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Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (!3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P!0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.

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Glucagon-like peptide-1 (GLP-1) receptors are not overexpressed in pancreatic islets from patients with severe hyperinsulinaemic hypoglycaemia following gastric bypass

Cited by 57 publications

References 12 publications

GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?

GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?

Molecular imaging in the investigation of hypoglycaemic syndromes and their management

Hypoglycemia in everyday life after gastric bypass and duodenal switch

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