General Information:

Id: 4,776
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mus musculus
article
Reference: Kruit JK et al.(2012) Loss of both ABCA1 and ABCG1 results in increased disturbances in islet sterol homeostasis, inflammation, and impaired beta-cell function Diabetes 61: 659-664 [PMID: 22315310]

Interaction Information:

Comment To determine whether ABCA1 and ABCG1 have complementary roles in beta-cells, mice lacking ABCG1 and beta-cell ABCA1 were generated. Lack of both ABCG1 and beta-cell ABCA1 resulted in increased fasting glucose levels and a greater impairment in glucose tolerance compared with either ABCG1 deletion or loss of ABCA1 in beta-cells alone.
Formal Description
Interaction-ID: 47265

gene/protein

ABCA1

affects_activity of

phenotype

hyperglycemia

after fasting
Drugbank entries Show/Hide entries for ABCA1
Comment To determine whether ABCA1 and ABCG1 have complementary roles in beta-cells, mice lacking ABCG1 and beta-cell ABCA1 were generated. Lack of both ABCG1 and beta-cell ABCA1 resulted in increased fasting glucose levels and a greater impairment in glucose tolerance compared with either ABCG1 deletion or loss of ABCA1 in beta-cells alone.
Formal Description
Interaction-ID: 47266

gene/protein

ABCG1

affects_activity of

phenotype

hyperglycemia

after fasting
Drugbank entries Show/Hide entries for ABCG1
Comment To determine whether ABCA1 and ABCG1 have complementary roles in beta-cells, mice lacking ABCG1 and beta-cell ABCA1 were generated. Lack of both ABCG1 and beta-cell ABCA1 resulted in increased fasting glucose levels and a greater impairment in glucose tolerance compared with either ABCG1 deletion or loss of ABCA1 in beta-cells alone.
Formal Description
Interaction-ID: 47267

gene/protein

ABCA1

affects_activity of

Drugbank entries Show/Hide entries for ABCA1
Comment To determine whether ABCA1 and ABCG1 have complementary roles in beta-cells, mice lacking ABCG1 and beta-cell ABCA1 were generated. Lack of both ABCG1 and beta-cell ABCA1 resulted in increased fasting glucose levels and a greater impairment in glucose tolerance compared with either ABCG1 deletion or loss of ABCA1 in beta-cells alone.
Formal Description
Interaction-ID: 47268

gene/protein

ABCG1

affects_activity of

Drugbank entries Show/Hide entries for ABCG1
Comment To determine whether ABCA1 and ABCG1 have complementary roles in beta-cells, mice lacking ABCG1 and beta-cell ABCA1 were generated. Glucose-stimulated insulin secretion was decreased and sterol accumulation increased in islets lacking both transporters compared with those isolated from knockout mice with each gene alone.
Formal Description
Interaction-ID: 47269

gene/protein

ABCA1

affects_activity of

in pancreas
Drugbank entries Show/Hide entries for ABCA1
Comment To determine whether ABCA1 and ABCG1 have complementary roles in beta-cells, mice lacking ABCG1 and beta-cell ABCA1 were generated. Glucose-stimulated insulin secretion was decreased and sterol accumulation increased in islets lacking both transporters compared with those isolated from knockout mice with each gene alone.
Formal Description
Interaction-ID: 47280

gene/protein

ABCG1

affects_activity of

in pancreas
Drugbank entries Show/Hide entries for ABCG1
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47281

gene/protein

ABCA1

affects_activity of

in pancreas
Drugbank entries Show/Hide entries for ABCA1
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47282

gene/protein

ABCG1

affects_activity of

in pancreas
Drugbank entries Show/Hide entries for ABCG1
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47284

gene/protein

ABCA1

affects_quantity of

drug/chemical compound

Cholesterol

in pancreas
Drugbank entries Show/Hide entries for ABCA1 or Cholesterol
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47285

gene/protein

ABCG1

affects_quantity of

drug/chemical compound

Cholesterol

in pancreas; in combination with ABCA1
Drugbank entries Show/Hide entries for ABCG1 or Cholesterol
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47286

gene/protein

ABCA1

NOT affects_quantity of

drug/chemical compound

Cholesterol

in blood plasma
Drugbank entries Show/Hide entries for ABCA1 or Cholesterol
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47287

gene/protein

ABCA1

affects_quantity of

drug/chemical compound

Desmosterol

in pancreas
Drugbank entries Show/Hide entries for ABCA1
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47288

gene/protein

ABCG1

affects_quantity of

drug/chemical compound

Desmosterol

in pancreas; in combination with ABCA1
Drugbank entries Show/Hide entries for ABCG1
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47289

gene/protein

ABCA1

affects_quantity of

drug/chemical compound

Cholestanol

in pancreas
Drugbank entries Show/Hide entries for ABCA1
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47290

gene/protein

ABCG1

affects_quantity of

drug/chemical compound

Cholestanol

in pancreas; in combination with ABCA1
Drugbank entries Show/Hide entries for ABCG1
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47291

gene/protein

ABCA1

affects_quantity of

drug/chemical compound

Campesterol

in pancreas
Drugbank entries Show/Hide entries for ABCA1
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47292

gene/protein

ABCG1

affects_quantity of

drug/chemical compound

Campesterol

in pancreas; in combination with ABCA1
Drugbank entries Show/Hide entries for ABCG1
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47293

gene/protein

ABCA1

affects_quantity of

drug/chemical compound

Sitosterol

in pancreas
Drugbank entries Show/Hide entries for ABCA1
Comment Loss of beta-cell ABCA1 resulted in significant islet cholesterol accumulation. Although ABCG1 deletion alone had no effect on cholesterol accumulation, combined loss of both transporters resulted in increased islet cholesterol levels compared with control. Other sterols, such as desmosterol, cholestanol, campesterol, and sitosterol were also increased in islets lacking both transporters. Importantly, plasma cholesterol levels were similar in all groups.
Formal Description
Interaction-ID: 47294

gene/protein

ABCG1

affects_quantity of

drug/chemical compound

Sitosterol

in pancreas; in combination with ABCA1
Drugbank entries Show/Hide entries for ABCG1
Comment Cholesterol accumulation in macrophages leads to activation of the unfolded protein response and CHOP-induced apoptosis. CHOP is an unfolded protein response-induced transcription factor that links endoplasmic reticulum stress to beta-cell dysfunction and apoptosis in animal models of type 2 diabetes. Beta-cell-specific deletion of ABCA1 caused a significant increase in CHOP expression in isolated islets, whereas ABCG1 deficiency had no effect. Lack of both transporters led to a further increase in CHOP expression, but this was not associated with any change in beta-cell mass at the time point studied.
Formal Description
Interaction-ID: 47295

gene/protein

ABCA1

affects_expression of

gene/protein

DDIT3

in pancreas
Drugbank entries Show/Hide entries for ABCA1
Comment Cholesterol accumulation in macrophages leads to activation of the unfolded protein response and CHOP-induced apoptosis. CHOP is an unfolded protein response-induced transcription factor that links endoplasmic reticulum stress to beta-cell dysfunction and apoptosis in animal models of type 2 diabetes. Beta-cell-specific deletion of ABCA1 caused a significant increase in CHOP expression in isolated islets, whereas ABCG1 deficiency had no effect. Lack of both transporters led to a further increase in CHOP expression, but this was not associated with any change in beta-cell mass at the time point studied.
Formal Description
Interaction-ID: 47296

gene/protein

ABCG1

affects_expression of

gene/protein

DDIT3

in pancreas; only in combination with ABCA1
Drugbank entries Show/Hide entries for ABCG1
Comment IL-1beta mRNA was significantly increased in islets lacking both ABCA1 and ABCG1, but not in islets lacking either ABCA1 or ABCG1 alone.
Formal Description
Interaction-ID: 47297

gene/protein

ABCA1

affects_expression of

gene/protein

IL1B

in pancreas; only in combination with ABCG1
Drugbank entries Show/Hide entries for ABCA1 or IL1B
Comment IL-1beta mRNA was significantly increased in islets lacking both ABCA1 and ABCG1, but not in islets lacking either ABCA1 or ABCG1 alone.
Formal Description
Interaction-ID: 47298

gene/protein

ABCG1

affects_expression of

gene/protein

IL1B

in pancreas; only in combination with ABCA1
Drugbank entries Show/Hide entries for ABCG1 or IL1B
Comment Loss of both beta-cell ABCA1 and ABCG1 leads to macrophage infiltration in pancreas.
Formal Description
Interaction-ID: 47299

gene/protein

ABCA1

affects_activity of

into pancreas; only in combination with ABCG1
Drugbank entries Show/Hide entries for ABCA1
Comment Loss of both beta-cell ABCA1 and ABCG1 leads to macrophage infiltration in pancreas.
Formal Description
Interaction-ID: 47300

gene/protein

ABCG1

affects_activity of

into pancreas; only in combination with ABCA1
Drugbank entries Show/Hide entries for ABCG1