Beneficial long-term antidiabetic actions of N- and C-terminally modified analogues of apelin-13 in diet-induced obese diabetic mice.

Vadivel Parthsarathy, C Hogg, Peter Flatt, Finbarr O'Harte

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

AimsThis study investigated the chronic effects of twice daily administration of stable apelin analogues, apelin-13 amide and (pGlu)apelin-13 amide, on metabolic parameters in glucose intolerant and insulin resistant diet-induced obese (DIO) mice fed a high-fat diet for 150 days.Study Design & MethodsGroups of mice received twice daily (09:00 and 17:00 h) injections of saline vehicle, apelin-13 amide, (pGlu)apelin-13 amide or exendin-4(1–39) for 28 days (all at 25 nmol/kg). Energy intake, body weight, non-fasting blood glucose, plasma insulin, glucose tolerance, metabolic response to feeding and insulin sensitivity together with pancreatic hormone content and biochemical parameters such as lipids and total GLP-1 were monitored. Dual-energy X-ray absorptiometry (DXA) analysis and indirect calorimetry were also performed.ResultsAdministration of apelin-13 amide, (pGlu)apelin-13 amide or exendin-4 significantly decreased bodyweight, food intake, blood glucose and increased plasma insulin compared with high-fat fed saline treated controls (P <0.05 and P <0.001), Additionally, all peptide treated groups exhibited improved glucose tolerance (oral and ip), metabolic responses to feeding and associated insulin secretion. (pGlu)apelin-13 amide also significantly improved HbA1c and insulin sensitivity after 28 days. Both (pGlu)apelin-13 amide and exendin-4 increased bone mineral content and decreased respiratory exchange ratio (RER), whereas only (pGlu)apelin-13 amide increased energy expenditure. All treatment groups displayed reduced circulating triglycerides and increased GLP-1 concentrations, although only (pGlu)apelin-13 amide significantly reduced LDL-cholesterol, total body fat, and increased pancreatic insulin content.ConclusionThese data indicate the therapeutic potential of stable apelin-13 analogues with effects equivalent to or better than exendin-4.
LanguageEnglish
Pages319-327
JournalDiabetes Obesity and Metabolism
Volume20
Issue number2
Early online date22 Aug 2017
DOIs
Publication statusE-pub ahead of print - 22 Aug 2017

Fingerprint

Obese Mice
Hypoglycemic Agents
Amides
Diet
Insulin
Glucagon-Like Peptide 1
Insulin Resistance
Blood Glucose
apelin-13 peptide
Pancreatic Hormones
Glucose
Indirect Calorimetry
Photon Absorptiometry
High Fat Diet
Glucose Tolerance Test
Energy Intake
Bone Density
LDL Cholesterol
Energy Metabolism
Adipose Tissue

Keywords

  • Apelin
  • diabetes
  • high fat fed mice
  • analogue

Cite this

@article{117bf03455a741d798db3812457b4378,
title = "Beneficial long-term antidiabetic actions of N- and C-terminally modified analogues of apelin-13 in diet-induced obese diabetic mice.",
abstract = "AimsThis study investigated the chronic effects of twice daily administration of stable apelin analogues, apelin-13 amide and (pGlu)apelin-13 amide, on metabolic parameters in glucose intolerant and insulin resistant diet-induced obese (DIO) mice fed a high-fat diet for 150 days.Study Design & MethodsGroups of mice received twice daily (09:00 and 17:00 h) injections of saline vehicle, apelin-13 amide, (pGlu)apelin-13 amide or exendin-4(1–39) for 28 days (all at 25 nmol/kg). Energy intake, body weight, non-fasting blood glucose, plasma insulin, glucose tolerance, metabolic response to feeding and insulin sensitivity together with pancreatic hormone content and biochemical parameters such as lipids and total GLP-1 were monitored. Dual-energy X-ray absorptiometry (DXA) analysis and indirect calorimetry were also performed.ResultsAdministration of apelin-13 amide, (pGlu)apelin-13 amide or exendin-4 significantly decreased bodyweight, food intake, blood glucose and increased plasma insulin compared with high-fat fed saline treated controls (P <0.05 and P <0.001), Additionally, all peptide treated groups exhibited improved glucose tolerance (oral and ip), metabolic responses to feeding and associated insulin secretion. (pGlu)apelin-13 amide also significantly improved HbA1c and insulin sensitivity after 28 days. Both (pGlu)apelin-13 amide and exendin-4 increased bone mineral content and decreased respiratory exchange ratio (RER), whereas only (pGlu)apelin-13 amide increased energy expenditure. All treatment groups displayed reduced circulating triglycerides and increased GLP-1 concentrations, although only (pGlu)apelin-13 amide significantly reduced LDL-cholesterol, total body fat, and increased pancreatic insulin content.ConclusionThese data indicate the therapeutic potential of stable apelin-13 analogues with effects equivalent to or better than exendin-4.",
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Beneficial long-term antidiabetic actions of N- and C-terminally modified analogues of apelin-13 in diet-induced obese diabetic mice. / Parthsarathy, Vadivel; Hogg, C; Flatt, Peter; O'Harte, Finbarr.

In: Diabetes Obesity and Metabolism, Vol. 20, No. 2, 22.08.2017, p. 319-327.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Beneficial long-term antidiabetic actions of N- and C-terminally modified analogues of apelin-13 in diet-induced obese diabetic mice.

AU - Parthsarathy, Vadivel

AU - Hogg, C

AU - Flatt, Peter

AU - O'Harte, Finbarr

PY - 2017/8/22

Y1 - 2017/8/22

N2 - AimsThis study investigated the chronic effects of twice daily administration of stable apelin analogues, apelin-13 amide and (pGlu)apelin-13 amide, on metabolic parameters in glucose intolerant and insulin resistant diet-induced obese (DIO) mice fed a high-fat diet for 150 days.Study Design & MethodsGroups of mice received twice daily (09:00 and 17:00 h) injections of saline vehicle, apelin-13 amide, (pGlu)apelin-13 amide or exendin-4(1–39) for 28 days (all at 25 nmol/kg). Energy intake, body weight, non-fasting blood glucose, plasma insulin, glucose tolerance, metabolic response to feeding and insulin sensitivity together with pancreatic hormone content and biochemical parameters such as lipids and total GLP-1 were monitored. Dual-energy X-ray absorptiometry (DXA) analysis and indirect calorimetry were also performed.ResultsAdministration of apelin-13 amide, (pGlu)apelin-13 amide or exendin-4 significantly decreased bodyweight, food intake, blood glucose and increased plasma insulin compared with high-fat fed saline treated controls (P <0.05 and P <0.001), Additionally, all peptide treated groups exhibited improved glucose tolerance (oral and ip), metabolic responses to feeding and associated insulin secretion. (pGlu)apelin-13 amide also significantly improved HbA1c and insulin sensitivity after 28 days. Both (pGlu)apelin-13 amide and exendin-4 increased bone mineral content and decreased respiratory exchange ratio (RER), whereas only (pGlu)apelin-13 amide increased energy expenditure. All treatment groups displayed reduced circulating triglycerides and increased GLP-1 concentrations, although only (pGlu)apelin-13 amide significantly reduced LDL-cholesterol, total body fat, and increased pancreatic insulin content.ConclusionThese data indicate the therapeutic potential of stable apelin-13 analogues with effects equivalent to or better than exendin-4.

AB - AimsThis study investigated the chronic effects of twice daily administration of stable apelin analogues, apelin-13 amide and (pGlu)apelin-13 amide, on metabolic parameters in glucose intolerant and insulin resistant diet-induced obese (DIO) mice fed a high-fat diet for 150 days.Study Design & MethodsGroups of mice received twice daily (09:00 and 17:00 h) injections of saline vehicle, apelin-13 amide, (pGlu)apelin-13 amide or exendin-4(1–39) for 28 days (all at 25 nmol/kg). Energy intake, body weight, non-fasting blood glucose, plasma insulin, glucose tolerance, metabolic response to feeding and insulin sensitivity together with pancreatic hormone content and biochemical parameters such as lipids and total GLP-1 were monitored. Dual-energy X-ray absorptiometry (DXA) analysis and indirect calorimetry were also performed.ResultsAdministration of apelin-13 amide, (pGlu)apelin-13 amide or exendin-4 significantly decreased bodyweight, food intake, blood glucose and increased plasma insulin compared with high-fat fed saline treated controls (P <0.05 and P <0.001), Additionally, all peptide treated groups exhibited improved glucose tolerance (oral and ip), metabolic responses to feeding and associated insulin secretion. (pGlu)apelin-13 amide also significantly improved HbA1c and insulin sensitivity after 28 days. Both (pGlu)apelin-13 amide and exendin-4 increased bone mineral content and decreased respiratory exchange ratio (RER), whereas only (pGlu)apelin-13 amide increased energy expenditure. All treatment groups displayed reduced circulating triglycerides and increased GLP-1 concentrations, although only (pGlu)apelin-13 amide significantly reduced LDL-cholesterol, total body fat, and increased pancreatic insulin content.ConclusionThese data indicate the therapeutic potential of stable apelin-13 analogues with effects equivalent to or better than exendin-4.

KW - Apelin

KW - diabetes

KW - high fat fed mice

KW - analogue

U2 - 10.1111/dom.13068

DO - 10.1111/dom.13068

M3 - Article

VL - 20

SP - 319

EP - 327

JO - Diabetes, Obesity and Metabolism

T2 - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1463-1326

IS - 2

ER -