Pancreatic polypeptide administration improves abnormal glucose metabolism in patients with chronic pancreatitis

F. Charles Brunicardi, Rochelle L. Chaiken, Alice S. Ryan, Neal E. Seymour, James A. Hoffmann, Harold E. Lebovitz, Ronald E. Chance, Ronald L. Gingerich, Dana K. Andersen, Dariush Elahi

Research output: Contribution to journalArticle

Abstract

Chronic pancreatitis (CP) is associated with lowered plasma levels and a blunted nutrient-induced release of pancreatic polypeptide (PP). To investigate the possible role of PP on glucose metabolism, we studied male patients with documented CP (n = 5) and obesity-matched control subjects (NL) (n = 6). Hepatic glucose production (HGP) and overall glucose disposal rates were determined by [3-3H]glucose infusion during a hyperinsulinemic- euglycemic clamp during three separate admissions. Basal rates of HGP were higher in CP patients. In response to an infusion of insulin (60 pmol · m- 2 · min-1), HGP fell 91 ± 5% in NL subjects but only 68 ± 8% in CP subjects (P <0.05). One month later, the clamp was repeated during the final 2 h of an 8-h infusion of bovine PP (2 pmol · kg-1 · min-1). HGP before the insulin infusion and its subsequent suppression (NL: 83 ± 5%; CP: 86 ± 15%) were nearly identical between groups. In follow-up studies 1 month after the PP infusion, HGP both basally and in response to insulin alone were similar to the first study. During oral glucose tolerance tests (OGTT) performed 18 h after the PP infusion, subjects with normal (n = 7) baseline OGTT responses showed no effect. All patients with diabetic (n = 3) or nondiagnostic (n = 1) OGTT responses, however, demonstrated lowered mean plasma glucose levels (~ -2.3 mmol/L; range: -0.6 to -7.2 mmol/L). OGTTs repeated 1 month after the PP treatment showed a return to pretreatment responses. We conclude that chronic pancreatitis accompanied by PP deficiency is associated with partial hepatic resistance both in the basal state and in response to hyperinsulinemia. This impairment is reversed after iv PP administration. PP deficiency may therefore play a role in the development of pancreatogenic diabetes caused by pancreatic injury.

Original languageEnglish (US)
Pages (from-to)3566-3572
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume81
Issue number10
DOIs
StatePublished - 1996
Externally publishedYes

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Pancreatic Polypeptide
Chronic Pancreatitis
Metabolism
Glucose
Glucose Tolerance Test
Liver
Insulin
Clamping devices
Glucose Clamp Technique
Hyperinsulinism
Plasmas
Medical problems
Obesity
Nutrients
Food

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Brunicardi, F. C., Chaiken, R. L., Ryan, A. S., Seymour, N. E., Hoffmann, J. A., Lebovitz, H. E., ... Elahi, D. (1996). Pancreatic polypeptide administration improves abnormal glucose metabolism in patients with chronic pancreatitis. Journal of Clinical Endocrinology and Metabolism, 81(10), 3566-3572. https://doi.org/10.1210/jc.81.10.3566

Pancreatic polypeptide administration improves abnormal glucose metabolism in patients with chronic pancreatitis. / Brunicardi, F. Charles; Chaiken, Rochelle L.; Ryan, Alice S.; Seymour, Neal E.; Hoffmann, James A.; Lebovitz, Harold E.; Chance, Ronald E.; Gingerich, Ronald L.; Andersen, Dana K.; Elahi, Dariush.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 81, No. 10, 1996, p. 3566-3572.

Research output: Contribution to journalArticle

Brunicardi, FC, Chaiken, RL, Ryan, AS, Seymour, NE, Hoffmann, JA, Lebovitz, HE, Chance, RE, Gingerich, RL, Andersen, DK & Elahi, D 1996, 'Pancreatic polypeptide administration improves abnormal glucose metabolism in patients with chronic pancreatitis', Journal of Clinical Endocrinology and Metabolism, vol. 81, no. 10, pp. 3566-3572. https://doi.org/10.1210/jc.81.10.3566
Brunicardi, F. Charles ; Chaiken, Rochelle L. ; Ryan, Alice S. ; Seymour, Neal E. ; Hoffmann, James A. ; Lebovitz, Harold E. ; Chance, Ronald E. ; Gingerich, Ronald L. ; Andersen, Dana K. ; Elahi, Dariush. / Pancreatic polypeptide administration improves abnormal glucose metabolism in patients with chronic pancreatitis. In: Journal of Clinical Endocrinology and Metabolism. 1996 ; Vol. 81, No. 10. pp. 3566-3572.
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abstract = "Chronic pancreatitis (CP) is associated with lowered plasma levels and a blunted nutrient-induced release of pancreatic polypeptide (PP). To investigate the possible role of PP on glucose metabolism, we studied male patients with documented CP (n = 5) and obesity-matched control subjects (NL) (n = 6). Hepatic glucose production (HGP) and overall glucose disposal rates were determined by [3-3H]glucose infusion during a hyperinsulinemic- euglycemic clamp during three separate admissions. Basal rates of HGP were higher in CP patients. In response to an infusion of insulin (60 pmol · m- 2 · min-1), HGP fell 91 ± 5{\%} in NL subjects but only 68 ± 8{\%} in CP subjects (P <0.05). One month later, the clamp was repeated during the final 2 h of an 8-h infusion of bovine PP (2 pmol · kg-1 · min-1). HGP before the insulin infusion and its subsequent suppression (NL: 83 ± 5{\%}; CP: 86 ± 15{\%}) were nearly identical between groups. In follow-up studies 1 month after the PP infusion, HGP both basally and in response to insulin alone were similar to the first study. During oral glucose tolerance tests (OGTT) performed 18 h after the PP infusion, subjects with normal (n = 7) baseline OGTT responses showed no effect. All patients with diabetic (n = 3) or nondiagnostic (n = 1) OGTT responses, however, demonstrated lowered mean plasma glucose levels (~ -2.3 mmol/L; range: -0.6 to -7.2 mmol/L). OGTTs repeated 1 month after the PP treatment showed a return to pretreatment responses. We conclude that chronic pancreatitis accompanied by PP deficiency is associated with partial hepatic resistance both in the basal state and in response to hyperinsulinemia. This impairment is reversed after iv PP administration. PP deficiency may therefore play a role in the development of pancreatogenic diabetes caused by pancreatic injury.",
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AU - Hoffmann, James A.

AU - Lebovitz, Harold E.

AU - Chance, Ronald E.

AU - Gingerich, Ronald L.

AU - Andersen, Dana K.

AU - Elahi, Dariush

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