GIP Does Not Potentiate the Antidiabetic Effects of GLP-1 in Hyperglycemic Patients With Type 2 Diabetes

Mentis, Nikolaos; Vardarli, İrfan; Köthe, L.; Holst, Jens J.; Deacon, Carolyn F.; Theodorakis, Michael J.; Meier, Juris J.; Nauck, Michael A.

doi:10.2337/db10-1332

Cited by 157 publications

(159 citation statements)

References 55 publications

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“…It was recently reported that GIP infusion antagonizes the glucagonostatic effects of GLP-1 in hyperglycemic patients with type 2 diabetes [8]. Although active GIP levels were increased by sitagliptin in the present subjects, glucagon levels were reduced, indicating that the glucagonostatic effect of increased GLP-1 was superior to the glucagonotropic effect of enhanced GIP activities.…”

Section: Discussioncontrasting

confidence: 43%

“…A glucagon suppressive effect is one of these possible mechanisms. However, since DPP-4 inhibitors augment plasma activities of both GLP-1 and GIP, the latter being capable of antagonizing the glucagonostatic effect of the former [8], it is not clear whether DPP-4 inhibitors cause glucagon suppression in hyperglycemic insulin-treated type 2 diabetes patients.…”

Section: Meal Tolerance Testmentioning

confidence: 99%

“…In subjects with type 2 diabetes, secretion of incretins appears to be largely unaltered [5,6]. The insulinotropic effect of GLP-1 is somewhat reduced yet preserved [2], while that of GIP is essentially absent in type 2 diabetes [2,7,8]. In addition, although GLP-1 suppresses glucagon secretion, GIP infusion has been demonstrated to antagonize the glucagonostatic effects of GLP-1 in type 2 diabetes [8].…”

mentioning

confidence: 99%

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Addition of sitagliptin or metformin to insulin monotherapy improves blood glucose control <i>via</i> different effects on insulin and glucagon secretion in hyperglycemic Japanese patients with type 2 diabetes

et al. 2015

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Section: Discussioncontrasting

confidence: 43%

Section: Meal Tolerance Testmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Addition of sitagliptin or metformin to insulin monotherapy improves blood glucose control <i>via</i> different effects on insulin and glucagon secretion in hyperglycemic Japanese patients with type 2 diabetes

et al. 2015

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“…In this study, insulin levels were higher for L-glutamine vs. placebo only after 90 min, at which time the plasma glucose had already peaked and was decreasing. Given the expected lag (60-90 min) between elevating insulin levels and observing its effect on glucose lowering, a full effect on blood glucose would not be seen till 150 min to 180 min after the glucose challenge, as demonstrated by Nauck's group [48], which is outside the observation range in this study. Notably, there was an expected lag between peak GLP-1 secretion (at approximately 30 min) and peak insulin secretion (at approximately 90 min) in this study.…”

Section: Discussioncontrasting

confidence: 53%

Colonic delivery of nutrients for management of blood glucose in type 2 diabetes patients

Szewczyk¹,

Giannone²,

Marcuard³

et al. 2017

FFHD

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Citation: Szewczyk J, Giannone J., Marcuard S., Kindel T, Tso P, and Nolan R. Colonic delivery of nutrients for management of blood glucose in type 2 diabetes patients. Functional Foods in Health and Disease 2017; 7(1):36-53 ABSTRACT Background: It is now widely accepted that bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) can resolve or improve type 2 diabetes mellitus. Postprandial glucagon-like peptide-1(GLP-1) increases after both RYGB and SG and blockade of the GLP-1 receptor suppresses the hypoglycemic effect post-operatively. The expedited delivery of nutrients, including L-glutamine and butyrate, to the distal small intestine and colon, where most GLP-1-secreting enteroendocrine L-cells are expressed, could explain this increase post-surgery. Pharmacological treatments that target nutrient-sensing receptors on L-cells may mimic the effects of bariatric surgeries and may ameliorate deficiencies in gut hormone responses involved in the regulation of glucose and satiety. In this study, we investigated the effects of the colonic delivery of L-glutamine and butyrate on GLP-1 secretion and glucose homeostasis in both a pre-clinical rodent model and clinical type 2 diabetes mellitus (T2DM).Results: Infusion of 4.4mg of sodium butyrate, compared to saline, into the colon of Zucker diabetic fatty (ZDF) rats increased GLP-1secretion in response to an intra-duodenal glucose challenge. In a chronic study, oral dosing of 40mg of sodium butyrate twice a day, formulated as colon-targeted sustained-release tablets, preserved glucose tolerance and insulin sensitivity in ZDF rats. In ten T2DM patients requiring oral anti-hyperglycemic agents, infusion of 1g of L-glutamine into the colon, compared to saline, increased plasma GLP-1 (p=0.017 at 30 min) and insulin (p<0.01 at 90min; p=0.001 at 120min; AUC p<0.005) after an oral glucose challenge. Similar infusion with butyrate significantly increased only insulin secretion at 120 min, compared to saline (p<0.05). Neither agent had an effect on glucose disposal. Conclusion:Targeted colonic delivery of L-glutamine and butyrate augments secretion of mealstimulated GLP-1 and insulin; L-glutamine was more efficacious in humans. Such an approach may be valuable for the management of hyperglycemia in T2DM patients. A chronic clinical study with colon-targeted sustained-release L-glutamine is required to validate this hypothesis.Key words: Diabetes, nutrients, gut hormones, GLP-1, secretagogues, glucose management. INTRODUCTIONIt has been widely reported that bariatric surgery developed to treat morbid obesity is very effective in resolving type 2 diabetes mellitus (T2DM). Post-prandial glucagon-like peptide-1 (GLP-1) increases after both Roux-en-Y gastric bypass (RYGB) [1], biliopancreatic diversion (BPD) [2], and sleeve gastrectomy (SG), and blockade of the GLP-1 receptor suppresses the hypoglycemic effect post-operatively [3]. In 2004, a review by Buchwald [4] reported the following: that 83.7 percent of T2DM cases were resolved after surge...

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“…However, during hyperglycemia GLP-1 is more insulinotropic than GIP. Importantly, in most cases, GLP-1 maintains its insulinotropic effect in diabetic patients, but not GIP [14][15][16][17].…”

Section: The Incretin Conceptmentioning

confidence: 99%

GLP-1, the Gut-Brain, and Brain-Periphery Axes

Cabou¹,

Burcelin²

2011

Rev Diabet Stud

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■ AbstractGlucagon-like peptide 1 (GLP-1) is a gut hormone which directly binds to the GLP-1 receptor located at the surface of the pancreatic β-cells to enhance glucose-induced insulin secretion. In addition to its pancreatic effects, GLP-1 can induce metabolic actions by interacting with its receptors expressed on nerve cells in the gut and the brain. GLP-1 can also be considered as a neuropeptide synthesized by neuronal cells in the brain stem that release the peptide directly into the hypothalamus. In this environment, GLP-1 is assumed to control numerous metabolic and cardiovascular functions such as insulin secretion, glucose production and utilization, and arterial blood flow. However, the exact roles of these two locations in the regulation of glucose homeostasis are not well understood. In this review, we highlight the latest experimental data supporting the role of the gutbrain and brain-periphery axes in the control of glucose homeostasis. We also focus our attention on the relevance of β-cell and brain cell targeting by gut GLP-1 for the regulation of glucose homeostasis. In addition to its action on β-cells, we find that understanding the physiological role of GLP-1 will help to develop GLP-1-based therapies to control glycemia in type 2 diabetes by triggering the gut-brain axis or the brain directly. This pleiotropic action of GLP-1 is an important concept that may help to explain the observation that, during their treatment, type 2 diabetic patients can be identified as 'responders' and 'non-responders'.

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GIP Does Not Potentiate the Antidiabetic Effects of GLP-1 in Hyperglycemic Patients With Type 2 Diabetes

Cited by 157 publications

References 55 publications

Addition of sitagliptin or metformin to insulin monotherapy improves blood glucose control <i>via</i> different effects on insulin and glucagon secretion in hyperglycemic Japanese patients with type 2 diabetes

Addition of sitagliptin or metformin to insulin monotherapy improves blood glucose control <i>via</i> different effects on insulin and glucagon secretion in hyperglycemic Japanese patients with type 2 diabetes

Colonic delivery of nutrients for management of blood glucose in type 2 diabetes patients

GLP-1, the Gut-Brain, and Brain-Periphery Axes

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