ArticleEndocrinology2018
Reducing Glucokinase Activity Restores Endogenous Pulsatility and Enhances Insulin Secretion in Islets From db/db Mice.
Article in Endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Contrasting Effects of Chronic Glucokinase Activation and Inhibition on Pancreatic Beta-Cell Function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Article
- Influence of Certain Natural Bioactive Compounds on Glycemic Control: A Narrative Review.Nutrients · 2025Review
- Targeting Protein Kinases to Protect Beta-Cell Function and Survival in Diabetes.International journal of molecular sciences · 2024Review
- Glycolytic enzymes in non-glycolytic web: functional analysis of the key players.Cell biochemistry and biophysics · 2024Review
- The nuclear localization sequence and C-terminus of parathyroid hormone-related protein regulate normal pancreatic islet development and function.General and comparative endocrinology · 2023Article
- Review
- Review
- β-Cell glucokinase expression was increased in type 2 diabetes subjects with better glycemic control.Journal of diabetes · 2023Article
- Recent Developments in Islet Biology: A Review With Patient Perspectives.Canadian journal of diabetes · 2023Review
- Brain Glucose Sensing and the Problem of Relative Hypoglycemia.Diabetes care · 2023Review
- Glucokinase Inhibition: A Novel Treatment for Diabetes?Diabetes · 2023Review
- Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells.Nature communications · 2022Article
- Similarities in Calcium Oscillations Between Neonatal Mouse Islets and Mature Islets Exposed to Chronic Hyperglycemia.Endocrinology · 2022Article
- Genetic Reduction of Glucose Metabolism Preserves Functional β-Cell Mass in KATP-Induced Neonatal Diabetes.Diabetes · 2022Article
- The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress.Endocrinology · 2021Review
- Postnatal maturation of calcium signaling in islets of Langerhans from neonatal mice.Cell calcium · 2021Article
- Reflections on undergraduate research mentoring.Biophysicist (Rockville, Md.) · 2020Article
- Chronic stimulation induces adaptive potassium channel activity that restores calcium oscillations in pancreatic islets in vitro.American journal of physiology. Endocrinology and metabolism · 2020Article
- Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells.International journal of endocrinology · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
An early sign of islet failure in type 2 diabetes (T2D) is the loss of normal patterns of pulsatile insulin release. Disruptions in pulsatility are associated with a left shift in glucose sensing that can cause excessive insulin release in low glucose (relative hyperinsulinemia, a hallmark of early T2D) and β-cell exhaustion, leading to inadequate insulin release during hyperglycemia. Our hypothesis was that reducing excessive glucokinase activity in diabetic islets would improve their function. Isolated mouse islets were exposed to glucose and varying concentrations of the glucokinase inhibitor d-mannoheptulose (MH) to examine changes in intracellular calcium ([Ca2+]i) and insulin secretion. Acutely exposing islets from control CD-1 mice to MH in high glucose (20 mM) dose dependently reduced the size of [Ca2+]i oscillations detected by fura-2 acetoxymethyl. Glucokinase activation in low glucose (3 mM) had the opposite effect. We then treated islets from male and female db/db mice (age, 4 to 8 weeks) and heterozygous controls overnight with 0 to 10 mM MH to determine that 1 mM MH produced optimal oscillations. We then used 1 mM MH overnight to measure [Ca2+]i and insulin simultaneously in db/db islets. MH restored oscillations and increased insulin secretion. Insulin secretion rates correlated with MH-induced increases in amplitude of [Ca2+]i oscillations (R2 = 0.57, P < 0.01, n = 10) but not with mean [Ca2+]i levels in islets (R2 = 0.05, not significant). Our findings show that correcting glucose sensing can restore proper pulsatility to diabetic islets and improved pulsatility correlates with enhanced insulin secretion.
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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 OpenQuestion graph.