Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes

Yasuhiko Matsumoto, Masaki Ishii, Yohei Hayashi, Shinya Miyazaki, Takuya Sugita, Eriko Matsumoto, Kazuhisa Sekimizu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1â €‰h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18â €‰h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes.

Original languageEnglish
Article number10722
JournalScientific reports
Volume5
DOIs
Publication statusPublished - May 29 2015
Externally publishedYes

Fingerprint

Bombyx
Type 2 Diabetes Mellitus
pioglitazone
Pharmaceutical Preparations
Hemolymph
Metformin
Fat Body
Glucose
Insulin
Diet
Glucose Intolerance
Glucose Tolerance Test
Heat-Shock Proteins
Hypoglycemic Agents
Protein Kinases
Adipose Tissue
Fasting
Phosphorylation
Phenotype

All Science Journal Classification (ASJC) codes

  • General

Cite this

Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes. / Matsumoto, Yasuhiko; Ishii, Masaki; Hayashi, Yohei; Miyazaki, Shinya; Sugita, Takuya; Matsumoto, Eriko; Sekimizu, Kazuhisa.

In: Scientific reports, Vol. 5, 10722, 29.05.2015.

Research output: Contribution to journalArticle

Matsumoto, Yasuhiko ; Ishii, Masaki ; Hayashi, Yohei ; Miyazaki, Shinya ; Sugita, Takuya ; Matsumoto, Eriko ; Sekimizu, Kazuhisa. / Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes. In: Scientific reports. 2015 ; Vol. 5.
@article{6dba37bf8e1a470cbe8d3b12ef80f5e3,
title = "Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes",
abstract = "We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1{\^a} €‰h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18{\^a} €‰h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes.",
author = "Yasuhiko Matsumoto and Masaki Ishii and Yohei Hayashi and Shinya Miyazaki and Takuya Sugita and Eriko Matsumoto and Kazuhisa Sekimizu",
year = "2015",
month = "5",
day = "29",
doi = "10.1038/srep10722",
language = "English",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes

AU - Matsumoto, Yasuhiko

AU - Ishii, Masaki

AU - Hayashi, Yohei

AU - Miyazaki, Shinya

AU - Sugita, Takuya

AU - Matsumoto, Eriko

AU - Sekimizu, Kazuhisa

PY - 2015/5/29

Y1 - 2015/5/29

N2 - We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1â €‰h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18â €‰h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes.

AB - We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1â €‰h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18â €‰h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes.

UR - http://www.scopus.com/inward/record.url?scp=84930670152&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930670152&partnerID=8YFLogxK

U2 - 10.1038/srep10722

DO - 10.1038/srep10722

M3 - Article

C2 - 26024298

AN - SCOPUS:84930670152

VL - 5

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 10722

ER -