Tissue expression of DPP-IV in obesity-diabetes and modulatory effects on peptide regulation of insulin secretion

McKillop, Aine; Stevenson, Claire L.; Moran, Brian M; Abdel-Wahab, Yasser; Flatt, Peter

doi:10.1016/j.peptides.2017.12.020

Cited by 16 publications

(9 citation statements)

References 40 publications

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“…1 A). The doses were selected on the basis of ameliorating milder genetic or high-fat-induced [ 32 ] but not STZ-induced [ 33 ] forms of diabetes, to elucidate the direct effects on islet cell plasticity. Food and fluid intake were assessed every 2 days, whereas blood glucose and body weight were assessed every 4 days.…”

Section: Methodsmentioning

confidence: 99%

Effects of first-line diabetes therapy with biguanides, sulphonylurea and thiazolidinediones on the differentiation, proliferation and apoptosis of islet cell populations

Sarnobat

Moffett

Flatt

et al. 2021

J Endocrinol Invest

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Aims Metformin, rosiglitazone and sulfonylureas enhance either insulin action or secretion and thus have been used extensively as early stage anti-diabetic medication, independently of the aetiology of the disease. When administered to newly diagnosed diabetes patients, these drugs produce variable results. Here, we examined the effects of the three early stage oral hypoglycaemic agents in mice with diabetes induced by multiple low doses of streptozotocin, focusing specifically on the developmental biology of pancreatic islets. Methods Streptozotocin-treated diabetic mice expressing a fluorescent reporter specifically in pancreatic islet α-cells were administered the biguanide metformin (100 mg/kg), thiazolidinedione rosiglitazone (10 mg/kg), or sulfonylurea tolbutamide (20 mg/kg) for 10 days. We assessed the impact of the treatment on metabolic status of the animals as well as on the morphology, proliferative potential and transdifferentiation of pancreatic islet cells, using immunofluorescence. Results The effect of the therapy on the islet cells varied depending on the drug and included enhanced pancreatic islet β-cell proliferation, in case of metformin and rosiglitazone; de-differentiation of α-cells and β-cell apoptosis with tolbutamide; increased relative number of β-cells and bi-hormonal insulin + glucagon + cells with metformin. These effects were accompanied by normalisation of food and fluid intake with only minor effects on glycaemia at the low doses of the agents employed. Conclusions Our data suggest that metformin and rosiglitazone attenuate the depletion of the β-cell pool in the streptozotocin-induced diabetes, whereas tolbutamide exacerbates the β-cell apoptosis, but is likely to protect β-cells from chronic hyperglycaemia by directly elevating insulin secretion.

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Section: Methodsmentioning

confidence: 99%

Effects of first-line diabetes therapy with biguanides, sulphonylurea and thiazolidinediones on the differentiation, proliferation and apoptosis of islet cell populations

Sarnobat

Moffett

Flatt

et al. 2021

J Endocrinol Invest

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“…Both SARS and SARS-CoV2 enter the body through angiotensin converting enzyme 2 (ACE2), while MERS uses dipeptidyl peptidase-IV (DPP4) as its receptor [5,6]. Both enzyme expression patterns change in diabetes, albeit in different ways, making the receptor proteins themselves an unlikely explanation for the elevated risk [7,8]. Instead, research focus is shifting more towards impairment of immune response in diabetes as a cause for risk elevation [9,10].…”

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confidence: 99%

Diabetes and COVID-19

Peric

Stulnig

2020

Wien Klin Wochenschr

114

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The current pandemic of SARS-CoV-2 coronavirus disease 2019 (COVID-19) is a particular challenge for diabetes patients. Diabetes mellitus predisposes to a particularly severe course of the disease and doubles the COVID-19 mortality risk due to pulmonary and cardiac involvement. In addition, diabetes patients often suffer from comorbidities which further worsen clinical outcomes. Glycemic control during infectious diseases is often suboptimal, and antidiabetic drugs and insulin therapy have to be adapted accordingly. On the other hand, access of diabetes patients to outpatient clinics are limited during the ongoing season urging alternative treatment options, particularly the implementation of novel telemedicine strategies. Hence, the opportunity of the COVID 19 crisis should be taken to make a significant step forward in the care for diabetes patients. Keywords Viral pneumonia • SARS-CoV2 • Diabetes complications • Diabetes therapy • Telemedicine SARS-CoV-2 infection and its relation to diabetes Coronavirus disease 2019 (COVID-19) is an infectious and communicable respiratory disease caused by the recently surfaced betacoronavirus severe respiratory Informed consent statement S. Peric and T.M. Stulnig have significantly contributed to the manuscript and have given their informed consent to be included as authors.

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“…However, the WP shot also increased the GLP-1 ACTIVE/TOTAL ratio suggesting an inhibitory effect on DPP-IV activity, although this was only evident in the lean cohort. Thus, our WP dose (15 g) may have been insufficient to inhibit DPP-IV activity in centrally obese individuals, which is unsurprising given that DPP-IV activity is elevated in obese states (58,59). This hypothesis is also coherent with previous findings in overweight people with well controlled T2D, where an increase in GLP-1 A C T I V E / T O T A L was observed after consumption of a WP preload at a dose three-fold greater than what was administered here (15 g vs 50 g) (21).…”

Section: Discussionmentioning

confidence: 99%

The Postprandial Glycaemic and Hormonal Responses Following the Ingestion of a Novel, Ready-to-Drink Shot Containing a Low Dose of Whey Protein in Centrally Obese and Lean Adult Males: A Randomised Controlled Trial

et al. 2021

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PurposeElevated postprandial glycaemia [PPG] increases the risk of cardiometabolic complications in insulin-resistant, centrally obese individuals. Therefore, strategies that improve PPG are of importance for this population. Consuming large doses of whey protein [WP] before meals reduces PPG by delaying gastric emptying and stimulating the secretion of the incretin peptides, glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide 1 [GLP-1]. It is unclear if these effects are observed after smaller amounts of WP and what impact central adiposity has on these gastrointestinal processes.MethodsIn a randomised-crossover design, 12 lean and 12 centrally obese adult males performed two 240 min mixed-meal tests, ~5–10 d apart. After an overnight fast, participants consumed a novel, ready-to-drink WP shot (15 g) or volume-matched water (100 ml; PLA) 10 min before a mixed-nutrient meal. Gastric emptying was estimated by oral acetaminophen absorbance. Interval blood samples were collected to measure glucose, insulin, GIP, GLP-1, and acetaminophen.ResultsWP reduced PPG area under the curve [AUC0–60] by 13 and 18.2% in the centrally obese and lean cohorts, respectively (both p <0.001). In both groups, the reduction in PPG was accompanied by a two-three-fold increase in GLP-1 and delayed gastric emptying. Despite similar GLP-1 responses during PLA, GLP-1 secretion during the WP trial was ~27% lower in centrally obese individuals compared to lean (p = 0.001). In lean participants, WP increased the GLP-1ACTIVE/TOTAL ratio comparative to PLA (p = 0.004), indicative of reduced GLP-1 degradation. Conversely, no treatment effects for GLP-1ACTIVE/TOTAL were seen in obese subjects.ConclusionPre-meal ingestion of a novel, ready-to-drink WP shot containing just 15 g of dietary protein reduced PPG in lean and centrally obese males. However, an attenuated GLP-1 response to mealtime WP and increased incretin degradation might impact the efficacy of nutritional strategies utilising the actions of GLP-1 to regulate PPG in centrally obese populations. Whether these defects are caused by an individual’s insulin resistance, their obese state, or other obesity-related ailments needs further investigation.Clinical Trial RegistrationISRCTN.com, identifier [ISRCTN95281775]. https://www.isrctn.com/.

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Tissue expression of DPP-IV in obesity-diabetes and modulatory effects on peptide regulation of insulin secretion

Cited by 16 publications

References 40 publications

Effects of first-line diabetes therapy with biguanides, sulphonylurea and thiazolidinediones on the differentiation, proliferation and apoptosis of islet cell populations

Effects of first-line diabetes therapy with biguanides, sulphonylurea and thiazolidinediones on the differentiation, proliferation and apoptosis of islet cell populations

Diabetes and COVID-19

The Postprandial Glycaemic and Hormonal Responses Following the Ingestion of a Novel, Ready-to-Drink Shot Containing a Low Dose of Whey Protein in Centrally Obese and Lean Adult Males: A Randomised Controlled Trial

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