Impaired glucose-induced glucagon suppression after partial ...

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Results Fasting glucose concentrations increased significantly after partial pancreatectomy, but the immediate rise in post-challenge glucose excursions was lower following the intervention (p < 0.0001; Fig. 1A; (18)). This was accompanied by significant reduction in both fasting and post-challenge insulin and C-peptide levels (p < 0.0001; Fig. 1B, D; (18)). There was also a significant improvement in the Matsuda index of insulin sensitivity (6.8 ± 0.6 to 8.6 ± 0.6, p = 0.005), whereas HOMA IR was unchanged (1.7 ± 0.2 vs. 1.6 ± 0.1, p = 0.35). Fasting glucagon levels tended to be lower after partial pancreatectomy (p = 0.11). Oral glucose ingestion elicited a significant decline in glucagon concentrations in the experiments carried out prior to surgery (p < 0.0001; Fig. 1C). Thus, the maximum suppression of glucagon levels from baseline was -39 ± 3 % before and -22 ± 4 % after surgery (p = 0.0017). Similarly, the difference between the mean glucagon concentrations after glucose ingestion and baseline values (� glucagon) was markedly reduced after surgery (p < 0.01; Fig 2). In order to determine, whether the impairment in glucose-induced glucagon suppression after partial pancreatectomy was secondary to the development of hyperglycaemia or rather due to the reduction in insulin secretion, the glucose-induced reductions in glucagon concentrations were correlated to the respective glucose, insulin and C-peptide levels. There was indeed a significant relationship between the increments in insulin and C-peptide levels after the glucose load and both the mean changes in glucagon levels after the glucose load (� glucagon) (Fig. 3). Interestingly, the associations of glucagon levels with insulin levels were greater than with C-peptide concentrations. In contrast, neither the fasting glucose levels (r = 0.21, p = 0.081), nor the mean post-challenge glucose concentrations (r = 0.023, p = 0.85) were related to the mean glucose-induced changes in glucagon levels (details not shown). When the patients were grouped according to the respective sort of pancreatic resection, the impairment in glucose-induced suppression of glucagon levels was apparent after both pancreatic head (n = 24; p < 0.001; Fig. 4A) and tail (n = 12; 0 < 0.05; Fig. 4B) resection. 8
However, after pancreatic head resection fasting glucagon concentrations were almost unchanged, whereas the post-operative glucagon concentrations were even higher compared to pre-operative levels from t = 90 to 150 min after the glucose drink. In contrast, pancreatic tail resection caused an ~45% reduction in fasting glucagon levels, and postoperative glucagon levels remained lower than before surgery at all subsequent time points after the glucose drink. Moreover, the individual impact of the hemipancreatectomy on glucagon concentrations seemed to differ to some extent between the different groups of patients studied. Thus, in patients undergoing surgery for the removal of pancreatic adenomas or extrapancreatic tumors, fasting glucagon levels were 31% lower after surgery, and the glucose-induced decline in glucagon levels was no longer detectable (Fig. 5A). In patients undergoing surgery for chronic pancreatitis, the overall concentrations of glucagon tended to be lower at all time points compared to the other patient groups, but the impairment in glucose-induced glucagon suppression was less apparent (Fig.5B). In patients treated for pancreatic carcinoma, fasting glucagon levels were 23% lower after the operation, but post-challenge glucagon levels tended to be even higher (Fig. 5C). 9
Page 1 and 2: J Clin Endocrin Metab. First publis
Page 3 and 4: Introduction: In health, glucose ho
Page 5 and 6: Materials and methods Study design
Page 7: assay (ELISA) from DAKOP Ltd., Camb
Page 11 and 12: cell secretion (34, 35). Consistent
Page 13 and 14: A number of previous studies in rat
Page 15 and 16: References: 1. Meier JJ, Butler PC
Page 17 and 18: 36. Robertson RP, Sutherland DE, Se
Page 19 and 20: Figure legends: Figure 1: Plasma co

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