Evidence mapPaperPMID 40108209Full record

ArticleScientific reports2025

Insights into GLP-1 and insulin secretion mechanisms in pasireotide-induced hyperglycemia highlight effectiveness of Gs-targeting diabetes treatment.

Junichiro Sato, Katsunori Manaka, Hirofumi Horikoshi, Maho Taguchi, Kazuki Harada, Takashi Tsuboi, Masaomi Nangaku, Taroh Iiri, Noriko Makita

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Junichiro SatoDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Katsunori ManakaDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Hirofumi HorikoshiDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Maho TaguchiDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Kazuki HaradaDepartment of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro, Tokyo, Japan.
Takashi TsuboiDepartment of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro, Tokyo, Japan.
Masaomi NangakuDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Taroh IiriDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.ORCID http://orcid.org/0009-0009-6632-0617
Noriko MakitaDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. norimakitky@gmail.com.

Funding

a Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science 19K08996a Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science 19K09034
6 · The paper itself

Abstract

Pasireotide frequently causes severe hyperglycemia; however, its detailed mechanism remains unknown. There are no published guidelines regarding the optimal management of pasireotide-induced hyperglycemia based on its pathophysiology. Herein, we successfully switched a patient with acromegaly from a dipeptidyl peptidase-4 (DPP-4) inhibitor to a glucagon-like peptide-1 (GLP-1) analog due to pasireotide-induced deterioration of glycemic control, and we examined the underlying mechanism for glycemic control. An in vitro study was conducted using pancreatic β-cell line, MIN-6, stably expressing GLP-1R (GLP-1R-MIN-6 cells) and intestinal L-cell line, GLUTag. High glucose levels and Gs-coupled receptor stimulation synergistically triggered insulin and GLP-1 secretion. Gs-coupled receptor stimulation primarily triggered GLP-1 secretion, which was amplified by high glucose levels in GLUTag cells. Pasireotide drastically inhibited GLP-1 secretion induced by Gs-coupled receptor stimulation through SSTR5-Gi-dependent inhibition of cAMP levels, suggesting that the main pathway was completely blocked. Furthermore, administering GLP-1 partially overcame the inhibitory effect of pasireotide in GLP-1R-MIN-6 cells, leading to a partial recovery of insulin secretion. The drastic inhibition of GLP-1 secretion via shutdown of the main pathway is the primary cause of pasireotide-induced hyperglycemia. GLP-1 analogs, rather than DPP-4 inhibitors, can spare pasireotide-induced depletion of endogenous GLP-1 and restore insulin secretion.

Indexed as

Glucagon-Like Peptide 1HyperglycemiaInsulinInsulin SecretionSomatostatinAnimalsCell LineDipeptidyl-Peptidase IV InhibitorsGlucagon-Like Peptide-1 ReceptorHumansInsulin-Secreting CellsMaleReceptors, SomatostatinDipeptidyl-Peptidase IV InhibitorsGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorInsulinpasireotideReceptors, SomatostatinSomatostatinsomatostatin receptor 5GLP-1GLP-1 analogGPCRsInsulinL-cellsPasireotide

Identifiers

PMID40108209
PMCPMC11923236

What Socratic holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.