Elevated insulin, proinsulin and insulin-like growth factor-binding protein-1 in liver disease

David L. Hwang, Shiao Ping Huang, Wuu Shyang Lan, Phillip D.K. Lee

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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 languageEnglish (US)
Pages (from-to)316-321
Number of pages6
JournalGrowth Hormone and IGF Research
Issue number6
StatePublished - Dec 2003
Externally publishedYes


  • Cirrhosis
  • Hepatocellular carcinoma
  • IGFBP-1
  • Insulin
  • Liver disease
  • Proinsulin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


Dive into the research topics of 'Elevated insulin, proinsulin and insulin-like growth factor-binding protein-1 in liver disease'. Together they form a unique fingerprint.

Cite this