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- Alsalim, Wathik, et al.
(author)
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Effect of single-dose DPP-4 inhibitor sitagliptin on β-cell function and incretin hormone secretion after meal ingestion in healthy volunteers and drug-naïve, well-controlled type 2 diabetes subjects
- 2018
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In: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 20:4, s. 1080-1085
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Journal article (peer-reviewed)abstract
- To explore the effects of a single dose of the DPP-4 inhibitor sitagliptin on glucose-standardized insulin secretion and β-cell glucose sensitivity after meal ingestion, 12 healthy and 12 drug-naïve, well-controlled type 2 diabetes (T2D) subjects (mean HbA1c 43mmol/mol, 6.2%) received sitagliptin (100mg) or placebo before a meal (525kcal). β-cell function was measured as the insulin secretory rate at a standardized glucose concentration and the β-cell glucose sensitivity (the slope between glucose and insulin secretory rate). Incretin levels were also monitored. Sitagliptin increased standardized insulin secretion, in both healthy and T2D subjects, compared to placebo, but without increasing β-cell glucose sensitivity. Sitagliptin also increased active glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) and reduced total (reflecting the secretion) GIP, but not total GLP-1 levels. We conclude that a single dose of DPP-4 inhibition induces dissociated effects on different aspects of β-cell function and incretin hormones after meal ingestion in both healthy and well-controlled T2D subjects.
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| 2. |
- Alsalim, Wathik, et al.
(author)
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Incretin and islet hormone responses to meals of increasing size in healthy subjects.
- 2015
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:2, s. 561-568
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Journal article (peer-reviewed)abstract
- Context: Postprandial glucose homeostasis is regulated through the secretion of glucagon-like peptide 1 (GLP-1) through stimulation of insulin secretion and inhibition of glucagon secretion. However, how these processes dynamically adapt to demands created by caloric challenges achieved during daily life is not known. Objective: To explore adaptation of incretin and islet hormones after mixed meals of increasing size in healthy subjects. Design: Twenty-four healthy lean subjects ingested a standard breakfast after an overnight fast followed, after four hours, by a lunch of different size (511, 743 and 1034 kcal) but with identical nutrient composition together with 1.5g paracetamol. Glucose, insulin, C-peptide, glucagon, intact glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and paracetamol were measured after the meals. Main outcome measure: Area under the 180 min curve (AUC) for insulin, C-peptide, glucagon, GLP-1 and GIP and model- derived ß-cell function and paracetamol appearance. Results: Glucose profiles were similar after the two larger meals whereas after the smaller meal, there was a post-peak reduction below baseline to nadir of 3.8±0.1mmol/l after 75min (p<0.001). AUC for GLP-1, GIP, insulin and C-peptide were significantly higher by increasing the caloric load as was β-cells sensitivity to glucose. In contrast, AUC glucagon was the same for all three meals, although there was an increase in glucagon after the postpeak glucose reduction in the smaller meal. The 0-20 min paracetamol appearance was increased by increasing meal size. Conclusion: Mixed lunch meals of increasing size elicit a caloric dependent insulin response due to increased β-cell secretion achieved by increased GIP and GLP-1 levels. The adaptation at larger meals results in identical glucose excursions, whereas after a lower caloric lunch the insulin response is high resulting in postpeak suppression of glucose below baseline.
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| 3. |
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| 4. |
- Tura, Andrea, et al.
(author)
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Increased insulin clearance in mice with double deletion of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors
- 2018
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In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 314:5, s. 639-646
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Journal article (peer-reviewed)abstract
- To establish whether incretin hormones affect insulin clearance, the aim of this study was to assess insulin clearance in mice with genetic deletion of receptors for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO). DIRKO (n = 31) and wild-type (WT) C57BL6J mice (n = 45) were intravenously injected with D-glucose (0.35 g/kg). Blood was sampled for 50 min and assayed for glucose, insulin, and C-peptide. Data were modeled to calculate insulin clearance; C-peptide kinetics was established after human C-peptide injection. Assessment of C-peptide kinetics revealed that C-peptide clearance was 1.66 ± 0.10 10–31/min. After intravenous glucose administration, insulin clearance during first phase insulin secretion was markedly higher in DIRKO than in WT mice (0.68 ± 0.06 10–3l/min in DIRKO mice vs. 0.54 ± 0.03 10–31/min in WT mice, P = 0.02). In contrast, there was no difference between the two groups in insulin clearance during second phase insulin secretion (P = 0.18). In conclusion, this study evaluated C-peptide kinetics in the mouse and exploited a mathematical model to estimate insulin clearance. Results showed that DIRKO mice have higher insulin clearance than WT mice, following intravenous injection of glucose. This suggests that incretin hormones reduce insulin clearance at physiological, nonstimulated levels.
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