Abstract
Insulin-like growth factor-binding protein-1 (IGFBP-1) is one of six soluble binding proteins that regulate the actions of the insulin-like growth factors (IGFs). Liver is the major source of IGFBP-1 in non-pregnant humans. In normal physiology, IGFBP-1 transcription is potently inhibited by insulin and serum levels are limited by a rapid clearance rate. Elevated levels of IGFBP-1 in liver disease have been attributed to insulin resistance; however, the relationships between these analytes have not been defined. We studied insulin, proinsulin and IGFBP-1 in normal subjects (NL, N = 47, 43 ± 12 yr), cirrhosis (CIR, N = 29, 54 ± 14 yr), hepatocellular carcinoma (HCC, N = 42, 61 ± 11 yr), and other liver tumors (TUM, N = 8, 60 ± 17 yr). All three analytes were significantly increased in liver disease (mean±SEM; p-values relative to normals): IGFBP-1 (NL 24 ± 4 ng/ml; CIR 235 ± 53, p < 0.0001: HCC 505 ± 105, p< 0.0001: TUM 118 ± 36, p< 0.0001), insulin (NL 72 ± 4 pM; CIR 261 ± 62, p < 0.0002; HCC 180 ± 25, p < 0.0001: TUM 189 ± 58, p < 0.0001), proinsulin (NL 6.5 ± 0.7 pM; CIR 36.8 ± 7.7, p < 0.0001; HCC 26.2 ± 3.8, p < 0.0001; TUM 32.1 ± 9.7, p < 0.0001). The ratio of proinsulin to insulin was also significantly elevated in liver disease. A typical curvilinear inverse relationship of insulin and IGFBP-1 was observed, but was shifted several fold higher for the liver disease groups. Our results demonstrate that insulin and proinsulin are elevated in liver disease. However, these elevations are paradoxically accompanied by elevated IGFBP-1 levels, indicating disruption of normal regulatory mechanisms. IGFBP-1 is postulated to play a dynamic role in metabolic substrate utilization via regulation of free IGF. Therefore, inappropriate elevation of IGFBP-1 could play an important role in the metabolic disturbances associated with liver disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 316-321 |
| Number of pages | 6 |
| Journal | Growth Hormone and IGF Research |
| Volume | 13 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2003 |
| Externally published | Yes |
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Keywords
- Cirrhosis
- Hepatocellular carcinoma
- IGFBP-1
- Insulin
- Liver disease
- Proinsulin
ASJC Scopus subject areas
- Endocrinology
- Endocrinology, Diabetes and Metabolism
Cite this
Elevated insulin, proinsulin and insulin-like growth factor-binding protein-1 in liver disease. / Hwang, David L.; Huang, Shiao Ping; Lan, Wuu Shyang; Lee, Phillip.
In: Growth Hormone and IGF Research, Vol. 13, No. 6, 12.2003, p. 316-321.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Elevated insulin, proinsulin and insulin-like growth factor-binding protein-1 in liver disease
AU - Hwang, David L.
AU - Huang, Shiao Ping
AU - Lan, Wuu Shyang
AU - Lee, Phillip
PY - 2003/12
Y1 - 2003/12
N2 - Insulin-like growth factor-binding protein-1 (IGFBP-1) is one of six soluble binding proteins that regulate the actions of the insulin-like growth factors (IGFs). Liver is the major source of IGFBP-1 in non-pregnant humans. In normal physiology, IGFBP-1 transcription is potently inhibited by insulin and serum levels are limited by a rapid clearance rate. Elevated levels of IGFBP-1 in liver disease have been attributed to insulin resistance; however, the relationships between these analytes have not been defined. We studied insulin, proinsulin and IGFBP-1 in normal subjects (NL, N = 47, 43 ± 12 yr), cirrhosis (CIR, N = 29, 54 ± 14 yr), hepatocellular carcinoma (HCC, N = 42, 61 ± 11 yr), and other liver tumors (TUM, N = 8, 60 ± 17 yr). All three analytes were significantly increased in liver disease (mean±SEM; p-values relative to normals): IGFBP-1 (NL 24 ± 4 ng/ml; CIR 235 ± 53, p < 0.0001: HCC 505 ± 105, p< 0.0001: TUM 118 ± 36, p< 0.0001), insulin (NL 72 ± 4 pM; CIR 261 ± 62, p < 0.0002; HCC 180 ± 25, p < 0.0001: TUM 189 ± 58, p < 0.0001), proinsulin (NL 6.5 ± 0.7 pM; CIR 36.8 ± 7.7, p < 0.0001; HCC 26.2 ± 3.8, p < 0.0001; TUM 32.1 ± 9.7, p < 0.0001). The ratio of proinsulin to insulin was also significantly elevated in liver disease. A typical curvilinear inverse relationship of insulin and IGFBP-1 was observed, but was shifted several fold higher for the liver disease groups. Our results demonstrate that insulin and proinsulin are elevated in liver disease. However, these elevations are paradoxically accompanied by elevated IGFBP-1 levels, indicating disruption of normal regulatory mechanisms. IGFBP-1 is postulated to play a dynamic role in metabolic substrate utilization via regulation of free IGF. Therefore, inappropriate elevation of IGFBP-1 could play an important role in the metabolic disturbances associated with liver disease.
AB - Insulin-like growth factor-binding protein-1 (IGFBP-1) is one of six soluble binding proteins that regulate the actions of the insulin-like growth factors (IGFs). Liver is the major source of IGFBP-1 in non-pregnant humans. In normal physiology, IGFBP-1 transcription is potently inhibited by insulin and serum levels are limited by a rapid clearance rate. Elevated levels of IGFBP-1 in liver disease have been attributed to insulin resistance; however, the relationships between these analytes have not been defined. We studied insulin, proinsulin and IGFBP-1 in normal subjects (NL, N = 47, 43 ± 12 yr), cirrhosis (CIR, N = 29, 54 ± 14 yr), hepatocellular carcinoma (HCC, N = 42, 61 ± 11 yr), and other liver tumors (TUM, N = 8, 60 ± 17 yr). All three analytes were significantly increased in liver disease (mean±SEM; p-values relative to normals): IGFBP-1 (NL 24 ± 4 ng/ml; CIR 235 ± 53, p < 0.0001: HCC 505 ± 105, p< 0.0001: TUM 118 ± 36, p< 0.0001), insulin (NL 72 ± 4 pM; CIR 261 ± 62, p < 0.0002; HCC 180 ± 25, p < 0.0001: TUM 189 ± 58, p < 0.0001), proinsulin (NL 6.5 ± 0.7 pM; CIR 36.8 ± 7.7, p < 0.0001; HCC 26.2 ± 3.8, p < 0.0001; TUM 32.1 ± 9.7, p < 0.0001). The ratio of proinsulin to insulin was also significantly elevated in liver disease. A typical curvilinear inverse relationship of insulin and IGFBP-1 was observed, but was shifted several fold higher for the liver disease groups. Our results demonstrate that insulin and proinsulin are elevated in liver disease. However, these elevations are paradoxically accompanied by elevated IGFBP-1 levels, indicating disruption of normal regulatory mechanisms. IGFBP-1 is postulated to play a dynamic role in metabolic substrate utilization via regulation of free IGF. Therefore, inappropriate elevation of IGFBP-1 could play an important role in the metabolic disturbances associated with liver disease.
KW - Cirrhosis
KW - Hepatocellular carcinoma
KW - IGFBP-1
KW - Insulin
KW - Liver disease
KW - Proinsulin
UR - http://www.scopus.com/inward/record.url?scp=0345602043&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0345602043&partnerID=8YFLogxK
U2 - 10.1016/S1096-6374(03)00042-X
DO - 10.1016/S1096-6374(03)00042-X
M3 - Article
VL - 13
SP - 316
EP - 321
JO - Endocrinology and Metabolism
JF - Endocrinology and Metabolism
SN - 1096-6374
IS - 6
ER -