ARA290 Improves Insulin Release and Glucose Tolerance in Type 2 Diabetic Goto-Kakizaki Rats.

Muller C, Yassin K, Li LS, Palmblad M, Efendic S, Berggren PO, Cerami A, Brines M, Östenson CG

Molecular medicine (Cambridge, Mass.)29 Dec 2015Cited by 10 (Europe PMC)

PMID26736179PMCIDPMC4818260DOI10.2119/molmed.2015.00267PepBankPUB-26736179

Summary

Effects of ARA290 on glucose homeostasis were studied in type 2 diabetic Goto-Kakizaki (GK) rats. In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity. Glucose-stimulated insulin secretion was increased in islets from ARA290-treated rats. Additionally, in response to glucose, carbachol and KCl, islet cytoplasmic free Ca²⁺ concentrations, [Ca²⁺]_i, were higher and the frequency of [Ca²⁺]_i oscillations enhanced compared with placebo. ARA290 also improved stimulus-secretion coupling for glucose in GK rat islets, as shown by an improved glucose oxidation rate, ATP production and acutely enhanced glucose-stimulated insulin secretion. ARA290 also exerted an effect distal to the ATP-sensitive potassium (K_ATP) channel on the insulin exocytotic pathway, since the insulin response was improved following islet depolarization by KCl when K_ATP channels were kept open by diazoxide. Finally, inhibition of protein kinase A completely abolished effects of ARA290 on insulin secretion. In conclusion, ARA290 improved glucose tolerance without affecting hematocrit in diabetic GK rats. This effect appears to be due to improved γ-cell glucose metabolism and [Ca²⁺]_i handling, and thereby enhanced glucose-induced insulin release.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study14

14 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In type 2 diabetic GK rats, daily ARA290 lowered plasma glucose after 3 and 4 weeks.
In plain wordsIn diabetic rats, ARA290 given daily lowered blood sugar after 3 and 4 weeks.
Peptide
Cibinetide (ARA-290)
Outcome
DecreasePlasma glucose at 3 and 4 weeks
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki (GK) rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · up to 4 weeksAs given in this study (rat).
Source sentences
Summary
plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
1 context sentence(design, population, supporting numbers)
Summary · context
In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
Show in the study text Report a problemFND-2673617901
02AnimalAnimal study (in vivo)Efficacy outcome
In type 2 diabetic GK rats, daily ARA290 reduced HbA1c by about 20%.
In plain wordsIn diabetic rats, ARA290 given daily lowered HbA1c, a long-term blood sugar marker, by about 20%.
Peptide
Cibinetide (ARA-290)
Outcome
DecreaseHemoglobin A1c
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki (GK) rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · up to 4 weeksAs given in this study (rat).
Measurements
HbA1c reduction
≈ 20%
ARA290-treated GK rats
Source sentences
Summary
hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
1 context sentence(design, population, supporting numbers)
Summary · context
In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
Show in the study text Report a problemFND-2673617902
03AnimalAnimal study (in vivo)Efficacy outcome
In type 2 diabetic GK rats, daily ARA290 did not change whole body insulin sensitivity.
In plain wordsIn diabetic rats, ARA290 did not change how well the whole body responds to insulin.
Peptide
Cibinetide (ARA-290)
Outcome
No significant changeWhole body insulin sensitivity
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki (GK) rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · up to 4 weeksAs given in this study (rat).
Source sentences
Summary
without changes in whole body and hepatic insulin sensitivity.
1 context sentence(design, population, supporting numbers)
Summary · context
In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
Show in the study text Report a problemFND-2673617903
04AnimalAnimal study (in vivo)Efficacy outcome
In type 2 diabetic GK rats, daily ARA290 did not change hepatic insulin sensitivity.
In plain wordsIn diabetic rats, ARA290 did not change how well the liver responds to insulin.
Peptide
Cibinetide (ARA-290)
Outcome
No significant changeHepatic insulin sensitivity
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki (GK) rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · up to 4 weeksAs given in this study (rat).
Source sentences
Summary
without changes in whole body and hepatic insulin sensitivity.
1 context sentence(design, population, supporting numbers)
Summary · context
In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
Show in the study text Report a problemFND-2673617904
05AnimalAnimal study (in vivo)Efficacy outcome
In type 2 diabetic GK rats, ARA290 improved glucose tolerance.
In plain wordsIn diabetic rats, ARA290 improved how the body handles a sugar load.
Peptide
Cibinetide (ARA-290)
Outcome
IncreaseGlucose tolerance
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki (GK) rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · up to 4 weeksAs given in this study (rat).
Source sentences
Summary
ARA290 improved glucose tolerance without affecting hematocrit in diabetic GK rats.
1 context sentence(design, population, supporting numbers)
Summary · context
In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
Show in the study text Report a problemFND-2673617905
06AnimalAnimal study (in vivo)Safety outcome
In type 2 diabetic GK rats, ARA290 did not affect hematocrit.
In plain wordsIn diabetic rats, ARA290 did not change hematocrit, the share of red cells in blood.
Peptide
Cibinetide (ARA-290)
Outcome
No significant changeHematocrit
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki (GK) rats
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated · up to 4 weeksAs given in this study (rat).
Source sentences
Summary
without affecting hematocrit in diabetic GK rats.
1 context sentence(design, population, supporting numbers)
Summary · context
In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
Show in the study text Report a problemFND-2673617906
07AnimalAnimal study (in vivo)Efficacy outcome
Islets from ARA290-treated GK rats showed increased glucose-stimulated insulin secretion.
In plain wordsIn rats, islets from ARA290-treated diabetic rats released more insulin in response to glucose.
Peptide
Cibinetide (ARA-290)
Outcome
IncreaseGlucose-stimulated insulin secretion in islets from treated rats
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki (GK) rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · up to 4 weeksAs given in this study (rat).
Source sentences
Summary
Glucose-stimulated insulin secretion was increased in islets from ARA290-treated rats.
1 context sentence(design, population, supporting numbers)
Summary · context
In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
Show in the study text Report a problemFND-2673617907
08AnimalAnimal study (in vivo)Efficacy outcome
In islets from GK rats, ARA290 raised islet cytoplasmic free calcium concentrations in response to glucose, carbachol and KCl compared with placebo.
In plain wordsIn rats, islets from ARA290-treated diabetic rats had higher calcium levels in response to glucose and other triggers than placebo islets.
Peptide
Cibinetide (ARA-290)
Outcome
IncreaseIslet cytoplasmic free Ca2+ concentration
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki (GK) rats
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · up to 4 weeksAs given in this study (rat).
Source sentences
Summary
in response to glucose, carbachol and KCl, islet cytoplasmic free Ca²⁺ concentrations, [Ca²⁺]_i, were higher and the frequency of [Ca²⁺]_i oscillations enhanced compared with placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
Show in the study text Report a problemFND-2673617908
09AnimalAnimal study (in vivo)Efficacy outcome
In islets from GK rats, ARA290 enhanced the frequency of islet calcium oscillations compared with placebo.
In plain wordsIn rats, islets from ARA290-treated diabetic rats showed more frequent calcium oscillations than placebo islets.
Peptide
Cibinetide (ARA-290)
Outcome
IncreaseFrequency of islet [Ca2+]i oscillations
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki (GK) rats
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · up to 4 weeksAs given in this study (rat).
Source sentences
Summary
the frequency of [Ca²⁺]_i oscillations enhanced compared with placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
Show in the study text Report a problemFND-2673617909
10AnimalAnimal study (in vivo)Efficacy outcome
In GK rat islets, ARA290 improved the glucose oxidation rate.
In plain wordsIn rat islets from diabetic rats, ARA290 improved how fast sugar is burned for energy.
Peptide
Cibinetide (ARA-290)
Outcome
IncreaseGlucose oxidation rate in islets
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki (GK) rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · up to 4 weeksAs given in this study (rat).
Source sentences
Summary
ARA290 also improved stimulus-secretion coupling for glucose in GK rat islets, as shown by an improved glucose oxidation rate, ATP production and acutely enhanced glucose-stimulated insulin secretion.
1 context sentence(design, population, supporting numbers)
Summary · context
In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
Show in the study text Report a problemFND-2673617910
11AnimalAnimal study (in vivo)Efficacy outcome
In GK rat islets, ARA290 improved ATP production.
In plain wordsIn rat islets from diabetic rats, ARA290 improved energy (ATP) production.
Peptide
Cibinetide (ARA-290)
Outcome
IncreaseATP production in islets
Study
ratn: not reported in source
type 2 diabetic Goto-Kakizaki (GK) rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · up to 4 weeksAs given in this study (rat).
Source sentences
Summary
ARA290 also improved stimulus-secretion coupling for glucose in GK rat islets, as shown by an improved glucose oxidation rate, ATP production and acutely enhanced glucose-stimulated insulin secretion.
1 context sentence(design, population, supporting numbers)
Summary · context
In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity.
Show in the study text Report a problemFND-2673617911
12LabEx vivo tissueEfficacy outcome
In GK rat islets, ARA290 acutely enhanced glucose-stimulated insulin secretion.
In plain wordsIn lab tests on islets from diabetic rats, ARA290 quickly increased insulin release in response to glucose.
Peptide
Cibinetide (ARA-290)
Outcome
IncreaseAcute glucose-stimulated insulin secretion in islets
Study
ratn: not reported in source
GK rat islets
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
ARA290 also improved stimulus-secretion coupling for glucose in GK rat islets, as shown by an improved glucose oxidation rate, ATP production and acutely enhanced glucose-stimulated insulin secretion.
1 context sentence(design, population, supporting numbers)
Summary · context
Effects of ARA290 on glucose homeostasis were studied in type 2 diabetic Goto-Kakizaki (GK) rats.
Show in the study text Report a problemFND-2673617912
13LabEx vivo tissueMechanism
In GK rat islets with KATP channels held open by diazoxide, ARA290 improved the insulin response to KCl depolarization, showing an effect distal to the KATP channel.
In plain wordsIn lab tests on islets from diabetic rats, ARA290 improved insulin release even with the KATP channel held open.
Peptide
Cibinetide (ARA-290)
Outcome
IncreaseInsulin response to KCl depolarization with diazoxide
Study
ratn: not reported in source
GK rat islets
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
ARA290 also exerted an effect distal to the ATP-sensitive potassium (K_ATP) channel on the insulin exocytotic pathway, since the insulin response was improved following islet depolarization by KCl when K_ATP channels were kept open by diazoxide.
1 context sentence(design, population, supporting numbers)
Summary · context
Effects of ARA290 on glucose homeostasis were studied in type 2 diabetic Goto-Kakizaki (GK) rats.
Show in the study text Report a problemFND-2673617913
14LabEx vivo tissueMechanism
In GK rat islets, inhibition of protein kinase A completely abolished the effects of ARA290 on insulin secretion.
In plain wordsIn lab tests on islets from diabetic rats, blocking protein kinase A removed the effect of ARA290 on insulin release.
Peptide
Cibinetide (ARA-290)
Outcome
Not applicableDependence of ARA290 insulin secretion effect on protein kinase A
Study
ratn: not reported in source
GK rat islets
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Finally, inhibition of protein kinase A completely abolished effects of ARA290 on insulin secretion.
1 context sentence(design, population, supporting numbers)
Summary · context
Effects of ARA290 on glucose homeostasis were studied in type 2 diabetic Goto-Kakizaki (GK) rats.
Show in the study text Report a problemFND-2673617914

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Version 2Current
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:13 UTC
First added · source update from Europe PMC

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