Glucagon‐like peptide‐1 receptor agonist exenatide has no acute effect on <scp>MRI</scp>‐measured exocrine pancreatic function in patients with type 2 diabetes: a randomized trial

Smits, Mark M.; Tonneijck, Lennart; Muskiet, Marcel H.A.; Kramer, Mark H. H.; Diamant, Michaëla; Bos, Indra C. Pieters-van den; Raalte, Daniël H. van; Cahen, Djuna L.

doi:10.1111/dom.12612

Cited by 6 publications

(8 citation statements)

References 50 publications

(66 reference statements)

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“…We found increased concentrations of lipase and amylase following treatment with liraglutide, which is in agreement with previous studies where both amylase and lipase have been consistently reported to increase after weeks of treatment 8,13,14 . However, controversies do exist regarding the acute effects (minutes to hour) of GLP‐1/GLP‐1RAs on pancreatic enzymes 14,16,28,29 . In one study by our group, we did not find any significant acute effect of high (pharmacological) doses of native GLP‐1, the primary N‐terminally truncated GLP‐1 metabolite or a dipeptidyl peptidase‐4–resistant GLP‐1RA on amylase and lipase in healthy individuals 14 .…”

Section: Discussionsupporting

confidence: 92%

“…8,13,14 However, controversies do exist regarding the acute effects (minutes to hour) of GLP-1/GLP-1RAs on pancreatic enzymes. 14,16,28,29 In one study by our group, we did not find any significant acute effect of high (phar- secretion from the exocrine pancreas, 28 in agreement with studies using porcine pancreas. 29 While the strengths of this study are that it was prospectively designed to assess pancreatic responses to liraglutide in vivo in humans using several complementary state-of-the-art techniques, there are also some limitations.…”

Section: Adverse Eventssupporting

confidence: 91%

“…In one study by our group, we did not find any significant acute effect of high (pharmacological) doses of native GLP‐1, the primary N‐terminally truncated GLP‐1 metabolite or a dipeptidyl peptidase‐4–resistant GLP‐1RA on amylase and lipase in healthy individuals 14 . Furthermore, a study evaluating the acute effect of exenatide during secretin‐stimulated MR cholangiopancreatography did not show any effect on secretion from the exocrine pancreas, 28 in agreement with studies using porcine pancreas 29 …”

Section: Discussionmentioning

confidence: 69%

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No effects of a 6‐week intervention with a glucagon‐like peptide‐1 receptor agonist on pancreatic volume and oedema in obese men without diabetes

Svane

Johannesen

Martinussen

et al. 2020

Diabetes Obesity Metabolism

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Aim To investigate the effect of a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), liraglutide, on pancreatic volume, oedema, cellularity and DNA synthesis in humans. Materials and Methods We performed an open‐label study in 14 obese men (age 38 ± 11 years, body mass index 32 ± 4 kg/m2) without diabetes. Subjects were examined at baseline, during titration (week 4) of liraglutide towards 3.0 mg/day, and 2 weeks after steady‐state treatment (week 6) of a final dose of liraglutide. The primary endpoint was pancreatic volume determined by magnetic resonance imaging. Secondary endpoints included pancreatic oedema and cellularity, positron emission tomography‐based [18F]fluorothymidine (FLT) uptake (DNA synthesis) and plasma pancreatic enzymes. Results Plasma amylase (+7 U/L [95% confidence intervals 3‐11], P < .01) and lipase (+19 U/L [7‐30], P < .01) increased during liraglutide treatment. Pancreatic volume did not change from baseline to steady state of treatment (+0.2 cm3 [−8‐8], P = .96) and no change in pancreatic cellular infiltration was found (P = .22). During titration of liraglutide, FLT uptake in pancreatic tissue increased numerically (+0.08 [0.00‐0.17], P = .0507). Conclusions Six weeks of treatment with liraglutide did not affect pancreatic volume, oedema or cellularity in obese men without diabetes.

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Section: Discussionsupporting

confidence: 92%

Section: Adverse Eventssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 69%

See 1 more Smart Citation

No effects of a 6‐week intervention with a glucagon‐like peptide‐1 receptor agonist on pancreatic volume and oedema in obese men without diabetes

Svane

Johannesen

Martinussen

et al. 2020

Diabetes Obesity Metabolism

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“…T2D is a chronic disease characterized by hyperglycemia, insulin resistance, defective insulin secretion and islet of Langerhans remodeling [ 28 , 29 , 32 , 33 ]. The intestinal incretin GLP-1 also regulates glucose homeostasis in response to dietary fat and carbohydrate intake [ 4 ] and GLP-1 receptor (GLP-1R) agonists have become valuable tools in T2D treatment [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

The GLP-1 receptor agonists exenatide and liraglutide activate Glucose transport by an AMPK-dependent mechanism

et al. 2016

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Aims/hypothesisPotentiation of glucose-induced insulin secretion is the main mechanism of exenatide (EXE) antidiabetic action, however, increased glucose utilization by peripheral tissues has been also reported. We here studied the effect of EXE on glucose uptake by skeletal muscle cells.Methods2-deoxy-glucose (2DG) uptake and intracellular signal pathways were measured in rat L6 skeletal muscle myotubes exposed to 100 nmol/l EXE for up to 48 h. Mechanisms of EXE action were explored by inhibiting AMPK activity with compound C (CC, 40 μmol/l) or siRNAs (2 μmol/l).ResultsTime course experiments show that EXE increases glucose uptake up to 48 h achieving its maximal effect, similar to that induced by insulin, after 20 min (2- vs 2.5-fold-increase, respectively). Differently from insulin, EXE does not stimulate: (i) IR β-subunit- and IRS1 tyrosine phosphorylation and binding to p85 regulatory subunit of PI-3kinase; (ii) AKT activation; and (iii) ERK1/2 and JNK1/2 phosphorylation. Conversely, EXE increases phosphorylation of α-subunit of AMPK at Thr172 by 2.5-fold (p < 0.01). Co-incubation of EXE and insulin does not induce additive effects on 2DG-uptake. Inhibition of AMPK with CC, and reduction of AMPK protein expression by siRNA, completely abolish EXE-induced 2DG-uptake. Liraglutide, another GLP-1 receptor agonist, also stimulates AMPK phosphorylation and 2DG-uptake. Moreover, EXE stimulates 2DG-uptake also by L6 myotubes rendered insulin-resistant with methylglyoxal. Finally, EXE also induces glucose transporter Glut-4 translocation to the plasma membrane.Conclusions/interpretationIn L6 myotubes, EXE and liraglutide increase glucose uptake in an insulin-independent manner by activating AMPK.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0985-7) contains supplementary material, which is available to authorized users.

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“…In order to achieve early diagnosis in diabetes, the development of pancreatic specific contrast agents became a hot topic. Among others, some contrast agents were used to target pancreatic beta cells for diabetes related research subjects, for instance, glucagon-like peptide-1 (GLP1) receptor and GLP1 analogues have been frequently studied in rodent diabetes imaging[ 25 , 26 ]. The micro-vascular changes in case of diabetes and pancreatic inflammation were also investigated[ 27 , 28 ].…”

Section: Current Status Of Rodent Pancreatic Imagingmentioning

confidence: 99%

Pancreatic imaging: Current status of clinical practices and small animal studies

Yin

Peeters

Feng

et al. 2017

WJM

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Different causative factors acting on the pancreas can result in diseases such as pancreatitis, diabetes and pancreatic tumors. The high incidence and mortality of pancreatic diseases have placed diagnostic imaging in a crucial position in daily clinical practice. In this mini-review article different pancreatic imaging techniques are discussed, from the standard clinical imaging modalities and state of the art clinical magnetic resonance imaging techniques to current situations in pre-clinical pancreatic imaging studies. In particular, the challenges of pre-clinical rodent pancreatic imaging are addressed, with both the image acquisition techniques and the post-processing methods for rodent pancreatic imaging elaborated.

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Glucagon‐like peptide‐1 receptor agonist exenatide has no acute effect on MRI‐measured exocrine pancreatic function in patients with type 2 diabetes: a randomized trial

Cited by 6 publications

References 50 publications

No effects of a 6‐week intervention with a glucagon‐like peptide‐1 receptor agonist on pancreatic volume and oedema in obese men without diabetes

No effects of a 6‐week intervention with a glucagon‐like peptide‐1 receptor agonist on pancreatic volume and oedema in obese men without diabetes

The GLP-1 receptor agonists exenatide and liraglutide activate Glucose transport by an AMPK-dependent mechanism

Pancreatic imaging: Current status of clinical practices and small animal studies

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