Poly‐GLP‐1, a novel long‐lasting glucagon‐like peptide‐1 polymer, ameliorates hyperglycaemia by improving insulin sensitivity and increasing pancreatic beta‐cell proliferation

Ma, Xiaowei; Hui, Hongxiang; Liu, Zhenguo; He, Gong-Hao; Hu, Jing; Meng, Jingru; Guan, Li; Luo, Xianghong

doi:10.1111/j.1463-1326.2009.01070.x

Cited by 16 publications

(10 citation statements)

References 55 publications

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“…[22][23][24][25] A recent study in pigs showed increased islet number and β-cell proliferation after RYGBP, in parallel with a rise in GLP-1, demonstrating the effect of RYGBP on the plasticity of the endocrine pancreas in this animal model. 43 Whether this is true in humans is unknown.…”

Section: Rygbp Alters Incretin Physiology Rygbp Enhances Incretin Relmentioning

confidence: 99%

“…21 Both GLP-1 and GIP have a trophic effect on the β-cell, as demonstrated in vitro and in vivo in rodent studies. [22][23][24][25] GLP-1 has other important physiological effects, including potentiation of GSIS in the post-prandial setting, suppression of glucagon, slowing of gastric emptying, decrease of body weight and favorable cardiovascular protection, 1,26 that makes it an attractive tool for the treatment of overweight or obese individuals with diabetes. The half-life of GLP-1 and GIP is only few minutes and both incretins are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4).…”

Section: Importance Of the Incretin Effect In Physiologymentioning

confidence: 99%

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Bariatric surgery and obesity: influence on the incretins

Laferrère

2016

Int J Obes Supp

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The gut hormone incretins have an important physiological role in meal-related insulin release and post-prandial glucose control. In addition to weight loss, the incretin hormones have a role in glucose control after bariatric surgery. The release of incretins, and specifically of glucagon-like peptide (GLP)-1, in response to the ingestion of nutrients, is greatly enhanced after gastric bypass (RYGBP). The rapid transit of food from the gastric pouch to the distal ileum is responsible for the greater GLP-1 release after RYGBP. The incretin effect on insulin secretion, or the greater insulin response to oral glucose compared to an isoglycemic intravenous glucose challenge, is severely impaired in patients with type 2 diabetes, but is recovered rapidly after RYGBP. The improvement in insulin secretion rate and β-cell sensitivity to oral glucose after RYGBP is mediated by endogenous GLP-1, and is abolished by exendin 9-39, a specific GLP-1 receptor antagonist. While calorie restriction and weight loss have major effects on the rapid and sustained improvement of fasted glucose metabolism, the enhanced incretin effect is a key player in post-prandial glucose control after RYGBP.

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Section: Rygbp Alters Incretin Physiology Rygbp Enhances Incretin Relmentioning

confidence: 99%

Section: Importance Of the Incretin Effect In Physiologymentioning

confidence: 99%

Bariatric surgery and obesity: influence on the incretins

Laferrère

2016

Int J Obes Supp

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“…Recombinant DNA technology is also of interest for the synthesis of tandem repeats of naturally occurring peptides, as a strategy for the high-yield synthesis of peptide drugs and antigens 6–10. Furthermore, polymerization of peptide drugs with intervening protease cleavable sequences has the potential to improve their pharmacokinetics and drug efficacy11,12. However, current methods for the polymerization of DNA suffer from one or more critical limitations: they (1) require numerous steps, (2) are difficult to parallelize, and (3) do not provide tunable control over a range of molecular weights, all of which greatly limit the ability to simultaneously synthesize multiple variants with a range of repeat units and compositions.…”

mentioning

confidence: 99%

“…An emerging strategy for temporally sustained peptide delivery involves peptide polymerization with intervening protease-cleavable linkers 11. However, as existing designs employed protease sites that are rapidly cleaved, these constructs still required repeated daily injections.…”

mentioning

confidence: 99%

A highly parallel method for synthesizing DNA repeats enables the discovery of ‘smart’ protein polymers

Amiram¹,

Quiroz²,

Callahan³

et al. 2011

Nature Mater

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Robust high-throughput synthesis methods are needed to expand the repertoire of repetitive protein-polymers for different applications. To address this need, we developed a new method, overlap-extension rolling circle amplification (OERCA), for the highly parallel synthesis of genes encoding repetitive protein-polymers. OERCA involves a single PCR-type reaction for the rolling circle amplification of a circular DNA template and simultaneous overlap extension by thermal cycling. We characterized the variables that control OERCA and demonstrated its superiority over existing methods, its robustness, throughput and versatility by synthesizing variants of elastin-like polypeptides (ELPs) and protease-responsive polymers of a glucagon-like peptide-1 analog. Despite the GC-rich, highly repetitive sequences of ELPs, we synthesized remarkably large genes without recursive ligation. OERCA also enabled us to discover “smart” biopolymers that exhibit fully reversible thermally responsive behavior. This powerful strategy generates libraries of repetitive genes over a wide and tunable range of molecular weights in a “one-pot” parallel format.

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“…A long chain polymer of GLP-1 that is slowly degraded in the circulation by endopeptidases is at an early stage of testing. 15 Delivery of GLP-1 analogues by buccal, oral, and nasal routes and dermal patches, rather than injections, is being investigated.…”

Section: Other Glp-1 Based Treatmentsmentioning

confidence: 99%