HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schmitz, O. Search for Related Content PubMed Articles by Schmitz, O. Social Bookmarking                What's this?

Response to Block

From the Department of Endocrinology, University Hospital of Aarhus, Aarhus, Denmark

I thank Dr. Block (1) for the interest in our article (2) and the editor for the opportunity to clarify the point raised. As stated several times in our article (RESULTS, Table 2, CONCLUSIONS), we define the early-phase period (i.e., where insulin secretory rates were calculated) as the initial 30 min of the prandial phase. The calculation of insulin secretion was as noted based on measurements of insulin and C-peptide, utilizing the classic combined model. Samples were drawn every 10 min during this part of the prandial period.

The cardinal issue in our article is the effect of the insulin secretagogue repaglinide on the meal-induced insulin secretion, which is influenced by several nutrients, release of incretin hormones, etc. In CONCLUSIONS we discuss twice the intravenous glucose-induced early-phase insulin release (presumably what Dr. Block refers to as acute-phase insulin release) to notice another important aspect of type 2 diabetes pathophysiology. In the same paragraph, meal-induced insulin release was discussed as it appears from the references. We felt that the message was clear and it was easy for the general reader to distinguish between these two issues.

The allegation of the authors trying to equate meal-induced insulin secretion to intravenously glucose-induced early-phase insulin secretion warrants a comment. Oral insulin secretagogues are developed to reduce glycemia during daily life conditions (e.g., meals), but of course in the interest of gaining insight into mode of action, it may be of relevance to explore their effects on unphysiological insulin challenges (e.g., intravenous glucose). The immediate insulin secretion elicited by the latter stimulus is now demonstrated to be related to a pool of insulin vesicles docked at the plasma membrane, whereas the early-phase insulin secretion after meal ingestion is probably ascribable to a combination of release from this pool and initially undocked vesicles.

So, to some extent, it may be two sides of the same coin. Both a reduced meal-induced and intravenously glucose-induced early-phase insulin secretion are abnormalities often present in healthy prediabetic individuals (3,4). Clearly the two modes of stimulating the ß-cell are only partially comparable. Nevertheless, our study deals with clinical pharmacology and insulin and glucose dynamics during daily life conditions of type 2 diabetic individuals after administration of an insulin secretagogue. In this context, we did not find it of relevance to compare this daily life condition in terms of insulin release with an (unphysiological) intravenous glucose challenge. One almost gets the impression from Dr. Block’s comment that restoration of intravenously glucose-induced insulin secretion is even more pivotal than restoring the daily-life, meal-induced, early-phase insulin secretion.

Moreover, it is important to state that our study drug (repaglinide) convincingly improved insulin secretion during the initial 30 min of the prandial periods, but we never reported that this took place within 10 min after administration. I kindly ask Dr. Block to read our article again to solve this misinterpretation.

Finally, I thank Dr. Block for giving us the opportunity to emphasize the importance of defining insulin secretion (e.g., early-phase, very early–phase, acute-phase, first-phase insulin secretion to a given challenge) very carefully.

Footnotes

Address correspondence to Dr. Ole Schmitz, Department of Endocrinology, University Hospital of Aarhus, 8000 Aarhus C, Denmark. E-mail: ole.schmitz{at}ickf.au.dv.

References

1. Block M: Response to Schmitz et al. (Letter). Diabetes Care 25:1490, 2002[Free Full Text]
   
2. Schmitz O, Lund S, Andersen PH, Jonler M, Porksen N: Optimizing insulin secretagogue therapy in patients with type 2 diabetes: a randomized double-blind study with repaglinide. Diabetes Care 25:342–346, 2002[Abstract/Free Full Text]
   
3. Knowles NG, Landchild MA, Fujimoto WY, Kahn SE: Insulin and amylin release are both diminished in first-degree relatives of subjects with type 2 diabetes. Diabetes Care 25:292–295, 2002[Abstract/Free Full Text]
   
4. Nyholm B, Walker M, Gravholt CH, Shearing PA, Sturis J, Alberti KGMM, Holst JJ, Schmitz O: Twenty-four-hour insulin secretion rates, circulating concentrations of fuel substrates and gut incretin hormones in healthy offspring of type 2 (non-insulin-dependent) diabetic parents: evidence of several aberrations. Diabetologia 42:1314–1323, 1999[Medline]
   

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schmitz, O. Search for Related Content PubMed Articles by Schmitz, O. Social Bookmarking                What's this?