KNMI'23 Climate Scenarios for the Netherlands: Storyline Scenarios of Regional Climate Change

Abstract This paper presents the methodology for the construction of the KNMI'23 national climate scenarios for the Netherlands. We have developed six scenarios, that cover a substantial part of the uncertainty in CMIP6 projections of future climate change in the region. Different sources of uncertainty are disentangled as much as possible, partly by means of a storyline approach. Uncertainty in future emissions is covered by making scenarios conditional on different SSP scenarios (SSP1‐2.6, SSP2‐4.5, and SSP5‐8.5). For each SSP scenario and time horizon (2050, 2100, 2150), we determine a global warming level based on the median of the constrained estimates of climate sensitivity from IPCC AR6. The remaining climate model uncertainty of the regional climate response at these warming levels is covered by two storylines, which are designed with a focus on the annual and seasonal mean precipitation response (a dry‐trending and wet‐trending variant for each SSP). This choice was motivated by the importance of future water management to society. For users with specific interests we provide means how to account for the impact of the uncertainty in climate sensitivity. Since CMIP6 GCM data do not provide the required spatial detail for impact modeling, we reconstruct the CMIP6 responses by resampling internal variability in a GCM‐RCM initial‐condition ensemble. The resulting climate scenarios form a detailed storyline of plausible future climates in the Netherlands. The data can be used for impact calculations and assessments by stakeholders, and will be used to inform policy making in different sectors of Dutch society

Cholinergic signaling mediates the effects of xenin-25 on secretion of pancreatic polypeptide but not insulin or glucagon in humans with impaired glucose tolerance.

We previously demonstrated that infusion of an intestinal peptide called xenin-25 (Xen) amplifies the effects of glucose-dependent insulinotropic polypeptide (GIP) on insulin secretion rates (ISRs) and plasma glucagon levels in humans. However, these effects of Xen, but not GIP, were blunted in humans with type 2 diabetes. Thus, Xen rather than GIP signaling to islets fails early during development of type 2 diabetes. The current crossover study determines if cholinergic signaling relays the effects of Xen on insulin and glucagon release in humans as in mice. Fasted subjects with impaired glucose tolerance were studied. On eight separate occasions, each person underwent a single graded glucose infusion- two each with infusion of albumin, Xen, GIP, and GIP plus Xen. Each infusate was administered ± atropine. Heart rate and plasma glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide (PP) levels were measured. ISRs were calculated from C-peptide levels. All peptides profoundly increased PP responses. From 0 to 40 min, peptide(s) infusions had little effect on plasma glucose concentrations. However, GIP, but not Xen, rapidly and transiently increased ISRs and glucagon levels. Both responses were further amplified when Xen was co-administered with GIP. From 40 to 240 min, glucose levels and ISRs continually increased while glucagon concentrations declined, regardless of infusate. Atropine increased resting heart rate and blocked all PP responses but did not affect ISRs or plasma glucagon levels during any of the peptide infusions. Thus, cholinergic signaling mediates the effects of Xen on insulin and glucagon release in mice but not humans

KNMI'23 national climate scenarios - background dataset

<p>Dataset associated with <strong>Van der Wiel et al. (202?): KNMI'23 climate scenarios for the Netherlands: storyline scenarios of regional climate change, Earth's Future</strong><i><strong>, in review</strong></i><strong>.</strong></p><p>This dataset contains the CMIP6 data and EC-Earth3/RACMO data that formed the basis for the KNMI'23 national climate scenarios for the Netherlands (<a href="http://www.knmi.nl/klimaatscenarios">www.knmi.nl/klimaatscenarios</a>). Full details on the methodology, including the origin of this dataset, can be found in the above referenced paper.</p><ul><li><strong>original_ensembles.tar.gz</strong> - Contains the original CMIP6, EC-Earth3 and RACMO-based time series for the NL and NL+RM regions, for all variables of interest (TAS, PR, PET, WBDEFICIT, RSDS, PR10DMAX). Additionally, for TAS also global-mean time series are provided. Data from the historical experiment and three SSP-scenario experiments (SSP1-2.6, SSP2-4.5, SSP5-8.5) are provided.</li><li><strong>resampled_ensembles.tar.gz</strong> - Contains resampled datasets of EC-Earth3 and RACMO data, for each scenario-time horizon combination (Ld,Ln,Md,Mn,Hd,Hn, and 2050,2100,2150). Again these are the NL and NL+RM regional mean time series, for the variables of interest.</li></ul><p>Final data products for the KNMI'23 national climate scenarios can be downloaded from <a href="https://klimaatscenarios-data.knmi.nl/">https://klimaatscenarios-data.knmi.nl/</a>.</p&gt

Xen amplifies the effects of GIP on ISRs.

<p>Graded glucose infusions (GGIs) with the saline control (Panels A-C) or atropine infusion (Panels D-F) were conducted. Plasma glucose (Panels A and D) and ISRs (Panels B and E) are shown for the indicated times before and during GGIs. The glucose infusion rate (GIR) at each 40 minute step is shown in white. Note that plasma glucose levels increase progressively even though glucose was administered in a step-wise fashion. Data from panels A and B are re-graphed in panel C whereas data from panels D and E are re-graphed in panel F. Symbols and error bars are eliminated in panels C and F for clarity. The rapid and transient increases in ISR in response to GIP and GIP plus Xen from 0–40 minutes (Panels B and E) are reflected by the initial spikes in ISRs (Panels C and F) that occur in the absence of a significant increase in plasma glucose levels. Values represent group means ± SEM.</p

Atropine inhibits pancreatic polypeptide release.

<p><u>Panels A and B</u>. Pancreatic polypeptide (PP) levels were measured at the indicated times before and during graded glucose infusions (GGIs) in the presence of the indicated peptide(s) and with infusion of saline (<u>Panel A</u>) or atropine (<u>Panel B</u>). Total (<u>Panel C</u>) and incremental <u>(Panel D</u>) AUCs from 0–240 minutes were calculated from data in panels A and B. Incremental and total AUCs were determined for each individual and values represent group means ± SEM. Significance was determined using the mixed effects model. <i>p</i> values for each peptide versus albumin alone are indicated within charts in Panels C and D. <i>p</i> values for the effects of atropine for each peptide infusate (or albumin control) are indicated below Panels C and D. The <i>p</i> values for infusate effects were calculated for all 8 treatments. Note that atropine infusion completely blocks all pancreatic polypeptide responses.</p

Atropine does not inhibit effects of peptides on ISRs.

<p>Incremental (Panels A and C) and total (Panels B and D) AUCs were calculated using data shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192441#pone.0192441.g006" target="_blank">Fig 6</a>. Baseline values (average from -50 to -30 min) were subtracted to calculate incremental AUCs. Outcomes were determined for each individual and values represent group means ± SEM. Significance was determined using the mixed effects model. <u>Panels A and B</u>: Data are for 0–40 min (Panels <i>A</i> and <i>B</i>). <u>Panels C and D</u>: Data are for 40–240 min. Values were calculated from the 40 to 240 ISR (i)AUCs for each individual divided by the 40 to 240 glucose (i)AUCs for the same individual. Values represent group means ± SEM.</p

Peptide levels during graded glucose infusions.

<p>Subjects were administered 8 different graded glucose infusions, each on a separate day. Each visit was separated by at least 2 weeks. Glucose and peptides were infused from 0 min to 240 min and atropine (or saline control) was infused from -30 to 240 min as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192441#pone.0192441.g002" target="_blank">Fig 2</a>. Steady state levels of immunoreactive-GIP (IR-GIP; panel A) and immunoreactive-Xen (IR-Xen; panel B) were measured during infusion with albumin alone (Alb), Xen alone, GIP alone, and the combination of GIP plus Xen (G+X). Each peptide was measured during infusion of atropine or the saline control. Because of limiting sample volumes, GIP and Xen were measured only in the 80 or 240 minute samples, respectively. Values represent group means ± SEM.</p

The graded glucose infusion protocol.

<p>The glucose infusion rate was increased in a step wise fashion every 40 minutes starting at time zero as shown in red. The primed-constant infusion of each peptide(s) was started at time zero and is shown in yellow. Note that GIP and Xen were each infused at the same rate when administered together. The primed-constant infusion of atropine (or saline) was initiated 30 minutes before the start of the graded glucose infusion as shown in blue. All infusions were terminated 240 minutes after the glucose infusion was initiated.</p

Flow diagram for atropine study.

<p>The flow diagram is for a crossover study in humans with impaired glucose tolerance and was designed so that each subject would receive all 8 graded glucose infusions. The same peptide(s) was administered during 2 successive visits- once with saline and once with atropine. First, the order of the peptide infusions was randomized. Second, the order of saline or atropine administration was randomized for each peptide. For example, if the subject was randomized to first receive Xen alone, this person would receive Xen in study visits 1 and 2. The atropine and saline infusions would then be randomized to visit 1 and 2. Eight subjects received all 8 graded glucose infusions. One subject received 6 infusions but did not receive either infusion with Xen alone. One subject received only the 2 infusions with GIP plus Xen.</p

Atropine does not inhibit the glucagon response to peptides.

<p>Data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192441#pone.0192441.g008" target="_blank">Fig 8A and 8B</a> representing the rapid and transient responses (0 to 40 minutes) were replotted. <u>Panel A:</u> Note that compared to albumin alone, the increase in plasma glucagon is highly significant during infusion of GIP+Xen from 5 to 40 minutes. Red #, *, **, and *** represent <i>p</i> <0.03, <0.01, <0.001, and <0.0001, respectively compared to albumin alone. The yellow + sign indicates a <i>p</i> value <0.07 for GIP alone compared to albumin alone. <u>Panels B-E</u>. Data from graded glucose infusions with albumin alone (Panel <i>B</i>), Xen alone (Panel C), GIP alone (Panel D) and GIP+Xen (Panel E) are shown for infusions with (red squares) and without (blue circles) atropine. Compared to the saline control, atropine had no statistically significant effect on the glucagon response to any of the 4 peptide treatments.</p