In vivo dual-delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP4) inhibitor through composites prepared by microfluidics for diabetes therapy

Abstract Although glucose is the best-known nutrient to stimulate glucagon-like peptide-1 (GLP-1) secretion, dietary peptides also potently stimulate GLP-1 secretion. Certain peptide fragments derived from dietary proteins possess dipeptidyl peptidase-4 (DPP-4) inhibitory activity in vitro. Hence, we hypothesised that dietary peptides protect GLP-1 from degradation through attenuating DPP-4 activity in vivo. Here, we compared GLP-1 responses with dietary proteins, a carbohydrate and a lipid (Intralipos) in rats having or not having plasma DPP-4 activity. Plasma GLP-1 concentrations clearly increased by oral administration of whey protein (2–4 g/kg), but not by that of dextrin (2–4 g/kg), in control rats (untreated Sprague–Dawley rats and F344/Jcl rats), having DPP-4 activity. In contrast, dextrin administration increased the plasma GLP-1 concentrations as the whey protein administration did, in rats having reduced or no DPP-4 activity (a DPP-4 inhibitor, sitagliptin-treated Sprague–Dawley rats or DPP-4-deficient F344/DuCrl/Crlj rats). DPP-4 inhibition by sitagliptin treatment also enhanced GLP-1 response to Intralipos, and casein, but the treatment did not further enhance GLP-1 response to whey protein. Intestinal GLP-1 content and gastric emptying rate were not associated with differences in GLP-1 responses to test nutrients. The luminal contents from rats administered whey protein decreased DPP-4 activity in vitro. These results suggest that GLP-1 released by dextrin, Intralipos and casein was immediately degraded by DPP-4, while GLP-1 released by whey protein was less degraded. Our study provides novel in vivo evidence supporting the hypothesis that dietary peptides not only stimulate GLP-1 secretion but also inhibit DPP-4 activity to potentiate GLP-1 response.

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Lack of preservation of insulin gene expression by a Glucagon-Like Peptide 1 agonist or a Dipeptidyl Peptidase 4 inhibitor in an in vivo model of glucolipotoxicity

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2009.12.020 ◽

2010 ◽

Vol 87 (3) ◽

pp. 322-328 ◽

Cited By ~ 6

Author(s):

Ghislaine Fontés ◽

Derek K. Hagman ◽

Martin G. Latour ◽

Meriem Semache ◽

Vincent Poitout

Keyword(s):

Gene Expression ◽

Dipeptidyl Peptidase ◽

Insulin Gene ◽

In Vivo Model ◽

Dipeptidyl Peptidase 4 ◽

Dipeptidyl Peptidase 4 Inhibitor ◽

Insulin Gene Expression ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Distinct effects of dipeptidyl peptidase-4 inhibitor and glucagon-like peptide-1 receptor agonist on islet morphology and function

Endocrine ◽

10.1007/s12020-015-0733-4 ◽

2015 ◽

Vol 51 (3) ◽

pp. 429-439 ◽

Cited By ~ 7

Author(s):

Asuka Morita ◽

Eri Mukai ◽

Ayano Hiratsuka ◽

Tomozumi Takatani ◽

Toshihiko Iwanaga ◽

...

Keyword(s):

Receptor Agonist ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase 4 ◽

Islet Morphology ◽

Dipeptidyl Peptidase 4 Inhibitor ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

And Function

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Combined treatment with dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin and elemental diets reduced indomethacin-induced intestinal injury in rats via the increase of mucosal glucagon-like peptide-2 concentration

Journal of Clinical Biochemistry and Nutrition ◽

10.3164/jcbn.14-111 ◽

2015 ◽

Vol 56 (2) ◽

pp. 155-162 ◽

Cited By ~ 7

Author(s):

Kaori Fujiwara ◽

Takuya Inoue ◽

Naoki Yorifuji ◽

Munetaka Iguchi ◽

Taisuke Sakanaka ◽

...

Keyword(s):

Combined Treatment ◽

Dipeptidyl Peptidase ◽

Intestinal Injury ◽

Dipeptidyl Peptidase 4 ◽

Dpp4 Inhibitor ◽

Elemental Diets ◽

Glucagon Like Peptide

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Glucagon-like peptide 1 and Glucagon-like peptide 2 in relation to osteoporosis in non-diabetic postmenopausal women

Scientific Reports ◽

10.1038/s41598-019-50117-z ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

María Cristina Montes Castillo ◽

María José Martínez Ramírez ◽

Rubén Soriano Arroyo ◽

Isabel Prieto Gomez ◽

Ana Belén Segarra Robles ◽

...

Keyword(s):

Postmenopausal Women ◽

Bone Remodeling ◽

Plasma Levels ◽

Dipeptidyl Peptidase ◽

Mineral Density ◽

Dipeptidyl Peptidase 4 ◽

Bone Remodeling Markers ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Osteoporosis Risk

Abstract Osteoporosis results from an imbalance in bone remodeling, which is known to follow a circadian rhythm determined by a functional relationship between intestine and bone tissue. Specific intestinal peptides have been identified as mediators. Glucagon-like peptide 1 and glucagon-like peptide 2, have been associated with bone health. Our main objective was to determine whether postprandial plasma levels of glucagon-like peptide 1, glucagon-like peptide 2 and dipeptidyl-peptidase 4 activity, are associated with osteoporosis in non-diabetic postmenopausal women. We studied non-diabetic postmenopausal women with osteoporosis diagnosed by dual-energy X-ray absorptiometry (cases, n = 43) and age-matched (±1 yr) controls without osteoporosis or a history of osteoporotic fracture (n = 43). We measured postprandial plasma levels of glucagon-like peptide 1, glucagon-like peptide 2, and dipeptidyl-peptidase 4 activity, bone mineral density, and baseline levels of bone remodeling markers and analyzed the food intake using a food-frequency questionnaire. Postprandial glucagon-like peptide 1 values were lower (p < 0.001) in cases, μ (SEM) = 116.25 (2.68), than in controls, μ (SEM) = 126.79 (2.68). Glucagon-like peptide 1 was associated with reduced osteoporosis risk in the crude logistic regression analysis [OR (95% CI) = 0.724 (0.53–0.97), p = 0.031] and adjusted analysis [OR = 0.603 (0.38–0.94), p = 0.027]. We found no association of glucagon-like peptide 2, or dipeptidyl-peptidase 4 activity with osteoporosis. Postprandial glucagon-like peptide 1 levels are related to osteoporosis and osteoporosis risk in non-diabetic postmenopausal women. Further studies are required to verify these findings.

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