Carbohydrate metabolism in non-insulin-dependent diabetes mellitus

S. Dinneen, J. Gerich, R. Rizza

Research output: Contribution to journalArticle

243 Citations (Scopus)

Abstract

The maintenance of normal carbohydrate tolerance requires the coordinated interaction of glucose, insulin, and glucagon. In the postabsorptive state the inhibitory effect of insulin on hepatic glycogenolysis and gluconeogenesis is precisely balanced by the stimulatory effect of glucagon. This ensures an adequate supply of glucose to insulin-independent tissues such as the brain. By limiting lipolysis, insulin also regulates the availability of free fatty acids. The rise in glucose that occurs after the ingestion of food stimulates the secretion of insulin and inhibits that of glucagon. These hormonal changes, as well as the modulatory effects of glucose itself, minimize the amount of glucose that must be metabolized by insulin-sensitive tissues (such as muscle) by enhancing hepatic glucose uptake and decreasing hepatic glucose release. At least in part because of insulin deficiency (relative or absolute), patients with diabetes mellitus have excessive hepatic release of glucose in both the postabsorptive and postprandial states. Although the level of glucose uptake is not appropriate for the prevailing glucose concentration, the absolute rate is equal to or greater than the rate in nondiabetic persons. Appropriately timed increases in the circulating insulin concentration are important determinants of hepatic and extrahepatic responses to ingested glucose. These considerations suggest that future efforts should be directed toward developing agents that increase early but not late postprandial plasma insulin concentrations and that restore a normal postprandial pattern of glucagon secretion. Agents that facilitate the suppression of hepatic glucose release and the stimulation of glucose uptake by insulin and glucose may also be of value. It is doubtful, however, that such agents will fully normalize postprandial carbohydrate metabolism without increasing the risk of hypoglycemia unless they also restore the dynamic interaction of glucose, insulin, and glucagon.

Original languageEnglish (US)
Pages (from-to)707-713
Number of pages7
JournalNew England Journal of Medicine
Volume327
Issue number10
StatePublished - 1992

Fingerprint

Carbohydrate Metabolism
Type 2 Diabetes Mellitus
Glucose
Insulin
Glucagon
Liver
Glycogenolysis
Gluconeogenesis
Lipolysis
Hypoglycemia
Nonesterified Fatty Acids
Diabetes Mellitus

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Dinneen, S., Gerich, J., & Rizza, R. (1992). Carbohydrate metabolism in non-insulin-dependent diabetes mellitus. New England Journal of Medicine, 327(10), 707-713.

Carbohydrate metabolism in non-insulin-dependent diabetes mellitus. / Dinneen, S.; Gerich, J.; Rizza, R.

In: New England Journal of Medicine, Vol. 327, No. 10, 1992, p. 707-713.

Research output: Contribution to journalArticle

Dinneen, S, Gerich, J & Rizza, R 1992, 'Carbohydrate metabolism in non-insulin-dependent diabetes mellitus', New England Journal of Medicine, vol. 327, no. 10, pp. 707-713.
Dinneen, S. ; Gerich, J. ; Rizza, R. / Carbohydrate metabolism in non-insulin-dependent diabetes mellitus. In: New England Journal of Medicine. 1992 ; Vol. 327, No. 10. pp. 707-713.
@article{184a64452f414619b8cce3fa89dc2b43,
title = "Carbohydrate metabolism in non-insulin-dependent diabetes mellitus",
abstract = "The maintenance of normal carbohydrate tolerance requires the coordinated interaction of glucose, insulin, and glucagon. In the postabsorptive state the inhibitory effect of insulin on hepatic glycogenolysis and gluconeogenesis is precisely balanced by the stimulatory effect of glucagon. This ensures an adequate supply of glucose to insulin-independent tissues such as the brain. By limiting lipolysis, insulin also regulates the availability of free fatty acids. The rise in glucose that occurs after the ingestion of food stimulates the secretion of insulin and inhibits that of glucagon. These hormonal changes, as well as the modulatory effects of glucose itself, minimize the amount of glucose that must be metabolized by insulin-sensitive tissues (such as muscle) by enhancing hepatic glucose uptake and decreasing hepatic glucose release. At least in part because of insulin deficiency (relative or absolute), patients with diabetes mellitus have excessive hepatic release of glucose in both the postabsorptive and postprandial states. Although the level of glucose uptake is not appropriate for the prevailing glucose concentration, the absolute rate is equal to or greater than the rate in nondiabetic persons. Appropriately timed increases in the circulating insulin concentration are important determinants of hepatic and extrahepatic responses to ingested glucose. These considerations suggest that future efforts should be directed toward developing agents that increase early but not late postprandial plasma insulin concentrations and that restore a normal postprandial pattern of glucagon secretion. Agents that facilitate the suppression of hepatic glucose release and the stimulation of glucose uptake by insulin and glucose may also be of value. It is doubtful, however, that such agents will fully normalize postprandial carbohydrate metabolism without increasing the risk of hypoglycemia unless they also restore the dynamic interaction of glucose, insulin, and glucagon.",
author = "S. Dinneen and J. Gerich and R. Rizza",
year = "1992",
language = "English (US)",
volume = "327",
pages = "707--713",
journal = "New England Journal of Medicine",
issn = "1533-4406",
publisher = "Massachussetts Medical Society",
number = "10",

}

TY - JOUR

T1 - Carbohydrate metabolism in non-insulin-dependent diabetes mellitus

AU - Dinneen, S.

AU - Gerich, J.

AU - Rizza, R.

PY - 1992

Y1 - 1992

N2 - The maintenance of normal carbohydrate tolerance requires the coordinated interaction of glucose, insulin, and glucagon. In the postabsorptive state the inhibitory effect of insulin on hepatic glycogenolysis and gluconeogenesis is precisely balanced by the stimulatory effect of glucagon. This ensures an adequate supply of glucose to insulin-independent tissues such as the brain. By limiting lipolysis, insulin also regulates the availability of free fatty acids. The rise in glucose that occurs after the ingestion of food stimulates the secretion of insulin and inhibits that of glucagon. These hormonal changes, as well as the modulatory effects of glucose itself, minimize the amount of glucose that must be metabolized by insulin-sensitive tissues (such as muscle) by enhancing hepatic glucose uptake and decreasing hepatic glucose release. At least in part because of insulin deficiency (relative or absolute), patients with diabetes mellitus have excessive hepatic release of glucose in both the postabsorptive and postprandial states. Although the level of glucose uptake is not appropriate for the prevailing glucose concentration, the absolute rate is equal to or greater than the rate in nondiabetic persons. Appropriately timed increases in the circulating insulin concentration are important determinants of hepatic and extrahepatic responses to ingested glucose. These considerations suggest that future efforts should be directed toward developing agents that increase early but not late postprandial plasma insulin concentrations and that restore a normal postprandial pattern of glucagon secretion. Agents that facilitate the suppression of hepatic glucose release and the stimulation of glucose uptake by insulin and glucose may also be of value. It is doubtful, however, that such agents will fully normalize postprandial carbohydrate metabolism without increasing the risk of hypoglycemia unless they also restore the dynamic interaction of glucose, insulin, and glucagon.

AB - The maintenance of normal carbohydrate tolerance requires the coordinated interaction of glucose, insulin, and glucagon. In the postabsorptive state the inhibitory effect of insulin on hepatic glycogenolysis and gluconeogenesis is precisely balanced by the stimulatory effect of glucagon. This ensures an adequate supply of glucose to insulin-independent tissues such as the brain. By limiting lipolysis, insulin also regulates the availability of free fatty acids. The rise in glucose that occurs after the ingestion of food stimulates the secretion of insulin and inhibits that of glucagon. These hormonal changes, as well as the modulatory effects of glucose itself, minimize the amount of glucose that must be metabolized by insulin-sensitive tissues (such as muscle) by enhancing hepatic glucose uptake and decreasing hepatic glucose release. At least in part because of insulin deficiency (relative or absolute), patients with diabetes mellitus have excessive hepatic release of glucose in both the postabsorptive and postprandial states. Although the level of glucose uptake is not appropriate for the prevailing glucose concentration, the absolute rate is equal to or greater than the rate in nondiabetic persons. Appropriately timed increases in the circulating insulin concentration are important determinants of hepatic and extrahepatic responses to ingested glucose. These considerations suggest that future efforts should be directed toward developing agents that increase early but not late postprandial plasma insulin concentrations and that restore a normal postprandial pattern of glucagon secretion. Agents that facilitate the suppression of hepatic glucose release and the stimulation of glucose uptake by insulin and glucose may also be of value. It is doubtful, however, that such agents will fully normalize postprandial carbohydrate metabolism without increasing the risk of hypoglycemia unless they also restore the dynamic interaction of glucose, insulin, and glucagon.

UR - http://www.scopus.com/inward/record.url?scp=0026795010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026795010&partnerID=8YFLogxK

M3 - Article

VL - 327

SP - 707

EP - 713

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 1533-4406

IS - 10

ER -