Consequences of systemic venous drainage and denervation of heterotopic pancreatic transplants for insulin/C-peptide profiles in the basal state and after oral glucose

Nauck, Michael A.; Büsing, M.; Siegel, E. G.; Talartschik, J.; Baartz, A.; Baartz, T.; Hopt, Ulrich T.; Becker, H. D.; Creutzfeldt, W.

doi:10.1007/bf00587626

Cited by 24 publications

(6 citation statements)

References 25 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Observations by other investigators [14,15] and ourselves [16] documented a similar degree of inhibition of plasma C-peptide concentrations in pancreas allograft recipients under the same experimental conditions, indicating the presence of a direct mechanism rather than a neural transmission. Furthermore, insulin receptors have been demonstrated on the pancreatic beta-cells [17].…”

Section: Discussionsupporting

confidence: 71%

Physiological Increase in Plasma Insulin Concentration Suppresses Proinsulin Secretion in Normal Controls but not in Subjects with Glucose Intolerance.

Wasada¹,

Kuroki²,

Arii³

et al. 1994

Endocr J

View full text Add to dashboard Cite

Abstract. Since insulin negatively controls its own secretion, we examined if insulin also inhibits the secretion of its precursor, proinsulin, in subjects with varying degrees of glucose tolerance. Under comparable hyperinsulinemia (50-70 µU/ml) achieved by the euglycemic insulin clamp technique, plasma C-peptide concentrations were equally suppressed to approximately 40-50% in nonobese subjects with normal glucose tolerance (NGT) (n=13, 35.5 ± 3.7%, M ± SEM), borderline glucose intolerance (BGI) (n=12, 46.7± 5.6%), and non-insulin-dependent diabetes mellitus (NIDDM) (n=12, 48.9 ± 5.4%). In contrast, plasma proinsulin concentrations were slightly but significantly suppressed in NGT (4.1 ± 0.2 to 3.7 ± 0.2 pmol /L, P<0.05), but not in patients with BGI (4.6 ± 0.3 to 4.8 ± 0.5 pmol /L, NS) and NIDDM (5.5 ±0.5 to 4.9±0.4 pmol/L, NS). The basal concentrations of proinsulin increased as glucose tolerance declined (P<0.05 between NGT and NIDDM).These results suggest that the basal secretion of proinsulin by beta-cells seems relatively insensitive to insulin compared with C-peptide, and that the insulin-proinsulin feedback loop is disturbed in glucoseintolerant subjects. Therefore, a defective feedback inhibition of proinsulin secretion by insulin may be partly involved in the disproportionate increase of plasma proinsulin concentrations in patients with NIDDM.

show abstract

Section: Discussionsupporting

confidence: 71%

Physiological Increase in Plasma Insulin Concentration Suppresses Proinsulin Secretion in Normal Controls but not in Subjects with Glucose Intolerance.

Wasada¹,

Kuroki²,

Arii³

et al. 1994

Endocr J

View full text Add to dashboard Cite

show abstract

“…It is of particular interest that the normal plasma glucose concentrations in pancreas transplant recipients occurred in the face of greatly increased basal plasma IRI and CPR concentrations. This is in agreement with other published data [8][9][10][15][16][17]21]. The increase in plasma CPR has been explained in terms of a combination of insulin resistance caused by prednisolone and alteration of C-peptide clearance secondary to impaired kidney function because CPR is cleared almost exclusively by the kidneys [22,23].…”

Section: Discussionsupporting

confidence: 92%

“…It is not clear whether insulin beta cell feedback normally plays a role in the establishment of basal insulin secretion rates. DeFronzo et al [1] reported that basal insulin secretion was effectively inhibited by a small (24 ± 3 pU/ml) physiological increase in the plasma insulin concentration in healthy subjects; that is in the range observed in pancreas-kidney transplant patients in the basal state [9,15,16,19]. We therefore suppose that the feedback inhibition of insulin secretion is defective in patients with a denervated, transplanted pancreas.…”

Section: Discussionmentioning

confidence: 75%

See 1 more Smart Citation

Insulin Sensitivity and Negative Insulin Feedback after Pancreas Transplantation in Insulin-Dependent Diabetic Patients.

Wasada¹,

Aoki²,

Babazono³

et al. 1995

Endocr J

View full text Add to dashboard Cite

Abstract. The aims of this study were to determine the change in the rate of insulin-stimulated glucose disposal (insulin sensitivity) and the ability of insulin to inhibit its own secretion in four pancreaskidney transplant recipients with insulin-dependent diabetes mellitus. Insulin sensitivity (glucose infusion rate, GIR) was measured by a euglycemic hyperinsulinemic clamp technique before and 2, 6 and 12 months after transplantation.The GIR values in the four recipients were normalized within 2 months and remained normal for 12 months after transplantation, despite long-term steroid therapy for immunosuppression.Physiological hyperinsulinemia (50-70 µU/ml) suppressed plasma C-peptide, but its nadirs were still higher than the basal levels in normal controls. Taking into account evidence of a minimal increase in the concentration of circulating insulin that inhibits insulin secretion in healthy subjects and evidence of increased insulin secretion in pancreas recipients, the authors speculate that defective feedback inhibition of insulin secretion could contribute, at least in part, to the disproportionate basal hyperinsulinemia in patients with a denervated, transplanted pancreas in the absence of insulin resistance.

show abstract

“…Under euglycemic conditions it was postulated that this elevation of insulin was due to an impaired insulin-insulin feedback inhibition that was neurally mediated [35][36][37]. The most likely mediator in this mechanism was the sympathetic nervous system innervating the pancreas [34].…”

Section: Discussionmentioning

confidence: 99%

Effect of Selective Denervation of the Rat Pancreas on Pancreatic Endocrine Function

Nilsson¹,

Zoucas²,

Lundquist

et al. 2001

Eur Surg Res

View full text Add to dashboard Cite

The purpose of this study was to investigate the influence of selective denervation of the rat pancreas on hormone secretion and on peripheral insulin sensitivity. Thirteen rats, 7 denervated and 6 sham operated, received an intravenous glucose challenge for 30 min. The basal plasma levels of insulin, glucagon and glucose did not differ between the two groups. An augmented insulin response to glucose was detected in the denervated group, whereas the glucagon response was unaffected. Glucose tolerance was marginally improved. Twenty-four rats, 12 denervated and 12 sham operated, received a constant infusion of glucose, insulin, epinephrine and propranolol in order to inhibit the endogenous insulin release and thus evaluate insulin sensitivity. No significant change in insulin sensitivity could be detected during our experimental conditions. We conclude that selective denervation brings about an increased insulin response to glucose, probably by interrupting a catecholaminergic negative tone on the β-cell. The sympathectomized animals did not disclose any apparent changes in peripheral insulin sensitivity.

show abstract

Consequences of systemic venous drainage and denervation of heterotopic pancreatic transplants for insulin/C-peptide profiles in the basal state and after oral glucose

Cited by 24 publications

References 25 publications

Physiological Increase in Plasma Insulin Concentration Suppresses Proinsulin Secretion in Normal Controls but not in Subjects with Glucose Intolerance.

Physiological Increase in Plasma Insulin Concentration Suppresses Proinsulin Secretion in Normal Controls but not in Subjects with Glucose Intolerance.

Insulin Sensitivity and Negative Insulin Feedback after Pancreas Transplantation in Insulin-Dependent Diabetic Patients.

Effect of Selective Denervation of the Rat Pancreas on Pancreatic Endocrine Function

Contact Info

Product

Resources

About