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February 1985, Vol 121, No. 2 >
Article | February 1985

Metabolic Importance of Acanthosis Nigricans

Jeffrey S. Flier, MD
Arch Dermatol. 1985;121(2):193-194. doi:10.1001/archderm.1985.01660020051015
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Acanthosis nigricans is a cutaneous lesion that has, in recent years, been of increasing interest to endocrinologists and diabetes specialists. What is the cause of the increased interest in this relatively uncommon skin lesion? The reason is the recognition that acanthosis nigricans is associated with a number of uncommon, but extremely interesting disorders characterized by cellular resistance to the action of insulin.1,2 In fact, acanthosis nigricans provides a major clinical clue to the existence of severe insulin resistance in many patients,3 and the lesion provides hints about the pathophysiologic basis of these syndromes.

What exactly is acanthosis nigricans? Clinically, it manifests as brown, velvety, hyperkeratotic plaques most often found in the axillae, the back of the neck, and other flexural areas.4 The lesions range in severity from minimal discoloration to extreme cases in which the entire surface of the skin may be involved. The pathologic changes are

REFERENCES

1 +
Kahn CR, Flier JS, Bar RS, et al:  The syndromes of insulin resistance and acanthosis nigricans: Insulin receptor disorders in man . N Engl Med 1976;;294:739-745.
2 +
Flier JS:  Insulin receptors and insulin resistance . Ann Rev Med 1983;;34:145-150.
3 +
Flier JS, Young JB, Langsberg L:  Familial insulin resistance with acanthosis nigricans, acral hypertrophy and muscle cramps: A new syndrome . N Engl J Med 1980;;390:970-973.
4 +
Fitzpatrick TB (ed): Dermatology in General Practice . New York, McGraw-Hill Book Co, 1979;.
5 +
Curth HO, Hilberg AW, Machacek GF, et al:  The site and histology of the cancer associated with acanthosis nigricans . Cancer 1962;;15:433-439.
6 +
Brown J, Winkelmann RK:  Acanthosis nigricans: Study of 90 cases . Medicine 1968;;47:33-56.
7 +
Lerner AB:  On the cause of acanthosis nigricans . N Engl J Med 1969;;281:106-107.
8 +
Flier JS, Kahn CR, Roth J, et al:  Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance . Science 1975;;190:53-64.
9 +
Podskalny JM, Kahn CR:  Cell culture studies on patients with extreme insulin resistance: I. Receptor defects in cultured fibroblasts . J Clin Endocrinol Metabol 1982;;54:261-268.
10 +
D'Ercole AJ, Underwood LE, Groelke J, et al:  Leprechaunism: Studies on the relationship among hyperinsulinemia, insulin resistance, and growth retardation . J Clin Endocrinol Metabol 1979;;48:495-502.
11 +
Flier JS, Eastman RC, Minaker KL, et al:  Acanthosis nigricans in obese women with hyperandrogenism: A marker for insulin resistance and distinction from the Type A and B syndromes . Diabetes , in press.
12 +
Kolterman OG, Insel J, Saekow M, et al:  Mechanisms of insulin resistance in human obesity: Evidence for receptor and postreceptor defects . J Clin Invest 1980;;65:1273-1284.
13 +
Flier JS, Roth J:  Diabetes in acromegaly and other endocrine disorders , in DeGroot LJ (ed): Endocrinology . New York, Grune & Stratton Inc, 1979;, pp 1085-1092.
14 +
Ober KP:  Acanthosis nigricans and insulin resistance associated with hypothyroidism . Arch Dermatol 1985;;121:229-231.
15 +
Kahn CR, Baird KL, Flier JS, et al:  Insulin receptors, receptor antibodies and the mechanism of insulin action . Recent Prog Horm Res 1981;;37:477-538.
16 +
Kasuga M, Karlsson FA, Kahn CR:  Insulin stimulates the phosphorylation of the 95,000 dalton subunit of its own receptor . Science 1982;;215:185-187.
17 +
Blundell TL, Bedarkian S, Humbel RE:  Tertiary structures, receptor binding, and antigenicity of insulin-like growth factors . Fed Proc 1983;;42:2592-2597.
18 +
Owen AJ, Pantazis P, Antoniades HN:  Simian sarcoma virus: Transformed cells secrete a mitogen identical to platelet-derived growth factor . Science 1984;;225:54-56.
19 +
Poretsky L, Seibel M, Smith D, et al:  Specific insulin binding sites in human ovarian stroma , J Clin Endocrinol Metabol 1984;;59:809-811.
20 +
Barbieri RL, Makris A, Ryan KJ:  Effects of insulin on steroidogenesis in cultured porcine ovarian theca . Fertil Steril 1983;;40:237-242.

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1 +
Kahn CR, Flier JS, Bar RS, et al:  The syndromes of insulin resistance and acanthosis nigricans: Insulin receptor disorders in man . N Engl Med 1976;;294:739-745.
2 +
Flier JS:  Insulin receptors and insulin resistance . Ann Rev Med 1983;;34:145-150.
3 +
Flier JS, Young JB, Langsberg L:  Familial insulin resistance with acanthosis nigricans, acral hypertrophy and muscle cramps: A new syndrome . N Engl J Med 1980;;390:970-973.
4 +
Fitzpatrick TB (ed): Dermatology in General Practice . New York, McGraw-Hill Book Co, 1979;.
5 +
Curth HO, Hilberg AW, Machacek GF, et al:  The site and histology of the cancer associated with acanthosis nigricans . Cancer 1962;;15:433-439.
6 +
Brown J, Winkelmann RK:  Acanthosis nigricans: Study of 90 cases . Medicine 1968;;47:33-56.
7 +
Lerner AB:  On the cause of acanthosis nigricans . N Engl J Med 1969;;281:106-107.
8 +
Flier JS, Kahn CR, Roth J, et al:  Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance . Science 1975;;190:53-64.
9 +
Podskalny JM, Kahn CR:  Cell culture studies on patients with extreme insulin resistance: I. Receptor defects in cultured fibroblasts . J Clin Endocrinol Metabol 1982;;54:261-268.
10 +
D'Ercole AJ, Underwood LE, Groelke J, et al:  Leprechaunism: Studies on the relationship among hyperinsulinemia, insulin resistance, and growth retardation . J Clin Endocrinol Metabol 1979;;48:495-502.
11 +
Flier JS, Eastman RC, Minaker KL, et al:  Acanthosis nigricans in obese women with hyperandrogenism: A marker for insulin resistance and distinction from the Type A and B syndromes . Diabetes , in press.
12 +
Kolterman OG, Insel J, Saekow M, et al:  Mechanisms of insulin resistance in human obesity: Evidence for receptor and postreceptor defects . J Clin Invest 1980;;65:1273-1284.
13 +
Flier JS, Roth J:  Diabetes in acromegaly and other endocrine disorders , in DeGroot LJ (ed): Endocrinology . New York, Grune & Stratton Inc, 1979;, pp 1085-1092.
14 +
Ober KP:  Acanthosis nigricans and insulin resistance associated with hypothyroidism . Arch Dermatol 1985;;121:229-231.
15 +
Kahn CR, Baird KL, Flier JS, et al:  Insulin receptors, receptor antibodies and the mechanism of insulin action . Recent Prog Horm Res 1981;;37:477-538.
16 +
Kasuga M, Karlsson FA, Kahn CR:  Insulin stimulates the phosphorylation of the 95,000 dalton subunit of its own receptor . Science 1982;;215:185-187.
17 +
Blundell TL, Bedarkian S, Humbel RE:  Tertiary structures, receptor binding, and antigenicity of insulin-like growth factors . Fed Proc 1983;;42:2592-2597.
18 +
Owen AJ, Pantazis P, Antoniades HN:  Simian sarcoma virus: Transformed cells secrete a mitogen identical to platelet-derived growth factor . Science 1984;;225:54-56.
19 +
Poretsky L, Seibel M, Smith D, et al:  Specific insulin binding sites in human ovarian stroma , J Clin Endocrinol Metabol 1984;;59:809-811.
20 +
Barbieri RL, Makris A, Ryan KJ:  Effects of insulin on steroidogenesis in cultured porcine ovarian theca . Fertil Steril 1983;;40:237-242.

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