Potential Therapeutic Levels of Glucagon-Like Peptide I Achieved in Humans by a Buccal Tablet

Gutniak, M.; Larsson, Hillevi; Heiber, S. J.; Juneskans, Olof T; Holst, Jens J.; Åhrén, Bo

doi:10.2337/diacare.19.8.843

Cited by 100 publications

(61 citation statements)

References 24 publications

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“…We have shown here that GLP-1 also stimulates the secretion of IAPP in humans. To raise circulating GLP-1, we used a buccal tablet consisting of 400 mg GLP-1, which has been shown to increase plasma GLP-1 levels to approximately 100-150 pmol/l within 30 min (31). These levels of GLP-1 are those required for its antidiabetogenic action (31,32) and, therefore, if GLP-1 were to be used in the treatment of type 2 diabetes, an accompanying increase in circulating IAPP would occur.…”

Section: Discussionmentioning

confidence: 99%

“…The placebo tablet consisted of the same tablet devoid of GLP-1. The detailed composition of the tablet has been described previously (31).…”

Section: Buccal Tabletmentioning

confidence: 99%

“…We analyzed serum insulin and IAPP levels after application of a 400 mg GLP-1 buccal tablet in seven healthy volunteers and in nine subjects with well-controlled type 2 diabetes. Buccal GLP-1 application has recently been shown to transiently increase plasma levels of GLP-1 to a peak level of 100-150 pmol/l, which is reached after 30 min followed by a decline with a circulating half-life of 26 min (31). This level of GLP-1 has been considered a potential therapeutic level of the peptide (31,32).…”

Section: Introductionmentioning

confidence: 99%

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No correlation between insulin and islet amyloid polypeptide after stimulation with glucagon-like peptide-1 in type 2 diabetes

Åhrén

Gutniak²

1997

European Journal of Endocrinology

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Objectives: To examine whether glucagon-like peptide-1 (GLP-1), which has been suggested as a new therapeutic agent in type 2 diabetes, affects circulating islet amyloid polypeptide (IAPP), a B-cell peptide of potential importance for diabetes pathophysiology. Design: GLP-1 was administered in a buccal tablet (400 mg) to seven healthy subjects and nine subjects with type 2 diabetes. Serum IAPP and insulin levels were measured before and after GLP-1 administration.Results: In the fasting state, serum IAPP was 4.1 Ϯ 0.3 pmol/l in the controls vs 9.8 Ϯ 0.9 pmol/l in the subjects with type 2 diabetes (P < 0.001). IAPP correlated with insulin only in controls (r=0.74, P ¼ 0.002) but not in type 2 diabetes (r ¼ 0.26, NS). At 15 min after GLP-1, circulating IAPP increased to 6.0Ϯ0.5 pmol/l in controls (P ¼ 0.009) and to 13.8Ϯ1.2 pmol/l in type 2 diabetes (P ¼ 0.021). In both groups, serum insulin increased and blood glucose decreased compared with placebo. In controls serum IAPP increased in parallel with insulin (r ¼ 0.79, P ¼ 0.032), whereas in type 2 diabetes the increase in IAPP did not correlate with the increase in insulin. Conclusion: Type 2 diabetes is associated with elevated circulating IAPP; GLP-1 stimulates IAPP secretion both in healthy human subjects and in type 2 diabetes; IAPP secretion correlates with insulin secretion only in healthy subjects and not in type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

“…The placebo tablet consisted of the same tablet devoid of GLP-1. The detailed composition of the tablet has been described previously (31).…”

Section: Buccal Tabletmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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No correlation between insulin and islet amyloid polypeptide after stimulation with glucagon-like peptide-1 in type 2 diabetes

Åhrén

Gutniak²

1997

European Journal of Endocrinology

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“…The results of this experiment were compared with the combined intravenous glucose plus GLP-1 stimulation in the same 8 patients and 7 healthy subjects (in 2 of the 8 patients, a GLP-1 injection without previous administration of glucose was performed instead of a combined glucose plus GLP-1 stimulation because FPG was 15 mmol/l). 10,15,20, 25, 30, 35, 40, 45, 47, 48, 49, 51, 53, 55, 60, 65, 70, 75, and 90 min after elevation of plasma glucose. The L-arginine was dissolved in 50 ml of sterilized water, dispensed into glass ampoules and stored at 4°C until the day of the experiment.…”

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confidence: 99%

Evaluation of beta-cell secretory capacity using glucagon-like peptide 1.

et al. 2000

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Abbreviations: ANOVA, analysis of variance; FPG, fasting plasma glucose; GLP-1, glucagon-like peptide 1; RIA, radioimmunoassay.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Evaluation of ␤-Cell Secretory Capacity Using Glucagon-Like Peptide 1 O R I G I N A L A R T I C L EOBJECTIVE -␤-Cell secretory capacity is often evaluated with a glucagon test or a meal test. However, glucagon-like peptide 1 (GLP-1) is the most insulinotropic hormone known, and the effect is preserved in type 2 diabetic patients.RESEARCH DESIGN AND METHODS -We first compared the effects of intravenous bolus injections of 2.5, 5, 15, and 25 nmol GLP-1 with glucagon (1 mg intravenous) and a standard meal (566 kcal) in 6 type 2 diabetic patients and 6 matched control subjects. Next, we studied another 6 patients and 6 control subjects and, in addition to the above procedure, performed a combined glucose plus GLP-1 stimulation, where plasma glucose was increased to 15 mmol/l before injection of 2.5 nmol GLP-1. Finally, we compared the insulin response to glucose plus GLP-1 stimulation with that observed during a hyperglycemic arginine clamp (30 mmol/l) in 8 patients and 8 control subjects.RESULTS -Peak insulin and C-peptide concentrations were similar after the meal, after 2.5 nmol GLP-1, and after glucagon. Side effects were less with GLP-1 than with glucagon. Peak insulin and C-peptide concentrations were as follows (C-peptide concentrations are given in parentheses): for patients (n = 12): meal, 277 ± 42 pmol/l (2,181 ± 261 pmol/l); GLP-1 (2.5 nmol), 390 ± 74 pmol/l (2,144 ± 254 pmol/l); glucagon, 329 ± 50 pmol/l (1,780 ± 160 pmol/l); glucose plus GLP-1, 465 ± 87 pmol/l (2,384 ± 2,99 pmol/l); for control subjects (n = 12): meal, 543 ± 89 pmol/l (2,873 ± 210 pmol/l); GLP-1, 356 ± 51 pmol/l (2,001 ± 130 pmol/l); glucagon, 420 ± 61 pmol/l (1,995 ± 99 pmol/l); glucose plus GLP-1, 1,412 ± 187 pmol/l (4,391 ± 416 pmol/l). Peak insulin and C-peptide concentrations during the hyperglycemic arginine clamp and during glucose plus GLP-1 injection were as follows: for patients: 475 ± 141 pmol/l (2,295 ± 379 pmol/l) and 816 ± 268 pmol/l (3,043 ± 508 pmol/l), respectively; for control subjects: 1,403 ± 308 pmol/l (4,053 ± 533 pmol/l) and 2,384 ± 452 pmol/l (6,047 ± 652 pmol/l), respectively.CONCLUSIONS -GLP-1 (2.5 nmol = 9 µg) elicits similar secretory responses to 1 mg glucagon (but has fewer side effects) and a standard meal. Additional elevation of plasma glucose to 15 mmol/l did not enhance the response further. The incremental response was similar to that elicited by arginine, but hyperglycemia had an additional effect on the response to arginine. E m e r g i n g T r e a t m e n t s a n d T e c h n o l o g i e s 808DIABETES CARE, VOLUME 23, NUMBER 6, JUNE 2000 , and a GLP-1 bolus injection of 2.5 nmol GLP-1 were performed. In addition, in type 2 diabetic patients with fasting plasma glucose (FPG) Ͻ15 mmol/l (9 of the 12 patients) and in all healthy subjects, a combine...

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“…It has been reported that GLP-1 administered via buccal tablets 119 nmol or via continuous infusion 2.16 nmol / kg per day for 2 days increases plasma GLP-1 concentrations in humans to a peak of 100−120 pmol / l 26,27 . Therefore, the combined use of DPP-4 inhibitors and GLP-1 could conceivably lead to higher plasma concentrations of GLP-1.…”

Section: Discussionmentioning

confidence: 99%

Glucagon-like Peptide-1 Suppresses the Proliferation and Migration of Vascular Smooth Muscle Cells: Implications for Preventive Effects on Atherosclerosis

Tomoyasu

Kim‐Kaneyama

Kohashi

et al. 2014

Showa Univ J Med Sci

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: Our group previously demonstrated the suppressive effect of glucagon-like peptide-1 GLP-1 on macrophage-driven atherosclerosis in apolipoprotein E-decient apoE / mice. In the present study we investigated the suppressive effect of GLP-1 on the atherogenic phenotype of vascular smooth muscle cells VSMCs in vivo using apoE / mice, and the proliferation and migration of human VSMCs in vitro. A 4-week infusion of GLP-1 in 17-week-old apoE / mice significantly reduced the proliferative VSMC phenotype stained with SMemb. Platelet-derived growth factor PDGF -BB signi cantly stimulated the proliferation of human aortic VSMCs by three fold. Both 0.1 and 1 nmol / l GLP-1 signi cantly suppressed the PDGF-induced VSMC proliferation, and this suppressive effect was significantly abolished by the GLP-1 receptor antagonist exendin 9−39 50 nmol / l . The GLP-1 receptor agonists liraglutide 100 nmol / l and exendin-4 100 nmol / l mimicked GLP-1, signi cantly suppressing PDGF-induced VSMC proliferation. PDGF-BB signi cantly stimulated the migration of human aortic VSMCs by 1.7 -fold, and this effect was signi cantly suppressed by 1 nmol / l GLP-1. These ndings suggest that GLP-1-related treatments may prevent the progression of atherosclerotic lesions by suppressing the proliferation and migration of VSMCs, which are characteristic features of atherosclerosis.

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Potential Therapeutic Levels of Glucagon-Like Peptide I Achieved in Humans by a Buccal Tablet

Abstract: Therapeutic plasma levels of GLP-I in humans were achieved after a single buccal tablet. No increased degradation of GLP-I was found in the buccal mucosa compared to subcutaneous tissue. This alternative treatment form may be feasible in in the future for NIDDM.

Cited by 100 publications

References 24 publications

No correlation between insulin and islet amyloid polypeptide after stimulation with glucagon-like peptide-1 in type 2 diabetes

No correlation between insulin and islet amyloid polypeptide after stimulation with glucagon-like peptide-1 in type 2 diabetes

Evaluation of beta-cell secretory capacity using glucagon-like peptide 1.

Glucagon-like Peptide-1 Suppresses the Proliferation and Migration of Vascular Smooth Muscle Cells: Implications for Preventive Effects on Atherosclerosis

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