ArticleDiabetes, obesity & metabolism2018
A vitamin B12 conjugate of exendin-4 improves glucose tolerance without associated nausea or hypophagia in rodents.
Article in Diabetes, obesity & metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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.
Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Glucagon-Like Peptide-1 Links Ingestion, Homeostasis, and the Heart.Comprehensive Physiology · 2025Review
- The agony and the efficacy: central mechanisms of GLP-1 induced adverse events and their mitigation by GIP.Frontiers in endocrinology · 2025Review
- A peptide triple agonist of GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors promotes glycemic control and weight loss.Scientific reports · 2023Article
- Chronic Semaglutide Treatment in Rats Leads to Daily Excessive Concentration-Dependent Sucrose Intake.Journal of the Endocrine Society · 2023Article
- Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects.Diabetes, obesity & metabolism · 2023Article
- Enteroendocrine cell regulation of the gut-brain axis.Frontiers in neuroscience · 2023Review
- Macronutrient intake: Hormonal controls, pathological states, and methodological considerations.Appetite · 2023Review
- The alpha-7 nicotinic acetylcholine receptor agonist GTS-21 does not affect food intake in rats.Pharmacology, biochemistry, and behavior · 2022Article
- Glucagon-like peptide-1 in diabetes care: Can glycaemic control be achieved without nausea and vomiting?British journal of pharmacology · 2022Review
- Brain GLP-1 and the regulation of food intake: GLP-1 action in the brain and its implications for GLP-1 receptor agonists in obesity treatment.British journal of pharmacology · 2022Review
- Review
- Synthesis, Optimization, and Biological Evaluation of Corrinated Conjugates of the GLP-1R Agonist Exendin-4.Journal of medicinal chemistry · 2021Article
- Review
- Therapeutic potential of α7 nicotinic acetylcholine receptor agonists to combat obesity, diabetes, and inflammation.Reviews in endocrine & metabolic disorders · 2020Review
- A second-generation glucagon-like peptide-1 receptor agonist mitigates vomiting and anorexia while retaining glucoregulatory potency in lean diabetic and emetic mammalian models.Diabetes, obesity & metabolism · 2020Article
- High-fat diet alters fluid intake without reducing sensitivity to glucagon-like peptide-1 receptor agonist effects.Physiology & behavior · 2020Article
- Corrination of a GLP-1 Receptor Agonist for Glycemic Control without Emesis.Cell reports · 2020Article
- GDF15 Induces Anorexia through Nausea and Emesis.Cell metabolism · 2020Article
- Systemically Administered Plant Recombinant Holo-Intrinsic Factor Targets the Liver and is not Affected by Endogenous B12 levels.Scientific reports · 2019Article
- Liraglutide pharmacotherapy reduces body weight and improves glycaemic control in juvenile obese/hyperglycaemic male and female rats.Diabetes, obesity & metabolism · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
aimsWhile pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 (B12) bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND
methodsWe evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice. To evaluate whether differences in the profile of effects of B12-Ex4 vs unconjugated Ex4 are the result of altered CNS penetrance, rats received systemic injections of fluorescein-Ex4 (Flex), Cy5-B12 or Cy5-B12-Ex4 and brain penetrance was evaluated using confocal microscopy. Uptake of systemically administered Cy5-B12-Ex4 in insulin-containing pancreatic beta cells was also examined.
resultsB12-Ex4 conjugate improves glucose tolerance, but does not elicit the malaise and anorexia produced by unconjugated Ex4. While Flex robustly penetrates into the brain (dorsal vagal complex, paraventricular hypothalamus), Cy5-B12 and Cy5-B12-Ex4 fluorescence were not observed centrally, supporting an absence of CNS penetrance, in line with observed reduction in CNS-associated Ex4 side effects. Cy5-B12-Ex4 colocalizes with insulin in the pancreas, suggesting direct pancreatic action as a potential mechanism underlying the hypoglycaemic effects of B12-Ex4.
conclusionThese novel findings highlight the potential clinical utility of B12-Ex4 conjugates as possible future T2DM therapeutics with reduced incidence of adverse effects.
Indexed as
Identifiers
What Socratic holds
Registered trials
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.