Blood sugar regulation by the liver and muscle

;;
;; This model is developed by Dr. Lin Xiang at the University of Kentucky. Contact: lin.xiang@uky.edu
;;
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;;
;; This model is free for classroom or virtual learning or teacher professional development related to STEM education.
;; You are asked to provide citations when using this model in any published work.
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breed [insulins insulin]
breed [glucose a-glucose]
breed [gluts glut]
breed [I-receptors I-receptor]
breed [G-receptors G-receptor]
breed [lipids lipid]
breed [glucagons glucagon]
breed [legends legend]

insulins-own [bonding]
patches-own[protein]
gluts-own[bonding name lock kind]
glucose-own [bonding cyto glycogen]
I-receptors-own [bonding]
G-receptors-own [bonding]
glucagons-own [bonding]

globals [clock]

to-report divider
  report patches with [pxcor = -6 and pycor > 2 and pycor < 8]
end 

to-report blood-sugar    ;all blood  sugar level are based on the concentration i.e., glocuse / patch
  report count glucose with [ycor > 2 and color = white and bonding = 0] * 100 /  (count patches with [pycor > 2 and pcolor = 0])
end 

to-report blood-sugar-l
  report count glucose with [xcor <= -6 and ycor > 2 and color = white and bonding = 0] * 100 / (count patches with [pxcor <= -6 and pycor > 2 and pcolor = 0])
end 

to-report blood-sugar-r
  report count glucose with [xcor > -6 and ycor > 2 and color = white and bonding = 0] * 100 / (count patches with [pxcor > -6 and pycor > 2 and pcolor = 0])
end 

to-report cyto-glucose-l
  report count glucose with [xcor <= -6 and ycor < 2 and color = white and bonding = 0 and glycogen = 0] * 100 / (count patches with [pxcor <= -6 and pycor < 2 and pcolor = 0])
end 

to-report cyto-glucose-r
  report count glucose with [xcor > -6 and ycor < 2 and color = white and bonding = 0 and glycogen = 0] * 100 / (count patches with [pxcor > -6 and pycor < 2 and pcolor = 0])
end 

to-report glycogen-level-l
  report count glucose with [xcor <= -6 and glycogen = 1 and color = 138]
end 

to-report glycogen-level-r
  report count glucose with [xcor > -6 and glycogen = 1 and color = 138]
end 

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;;                                                                           ;;
;;         Main Procedures (SETUP and GO)                                    ;;
;;                                                                           ;;
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to setup
 ;clear-turtles
 ;clear-patches
ca
 setup-legend     ; must be the first line
 setup-membrane-IR
 setup-glucose
 check-glucose-location
 setup-glut-4
 setup-glut-2
 setup-g-receptors
 set-insulin-sensitivity


reset-ticks
end 

to go
 if blood-sugar < 54 [user-message "The average blood sugar level is dangerously low." Stop]

adjust-glucose-location
check-glucose-location
set-insulin-sensitivity
setup-insulin
setup-glucagon
glucose-movement
insulin-movement
glut-4-movement
recover-lipids
glucagon-movement
glycolysis
glycogenesis-glycogenolysis
food-intake

plot-levels

tick
end 



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;;                                                                           ;;
;;         Sub-procedures of SETUP                                           ;;
;;                                                                           ;;
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to setup-membrane-IR

;make the membrane
  ask patches with [pycor = 2] [set pcolor 49 ]

; make boundary for the system
  ask patches with [abs pxcor = max-pxcor or abs pycor = max-pycor] [set pcolor 2]
  ask patches with [pycor <= min-pycor + 4 ] [set pcolor 2]
  ask patches with [pxcor = -6] [set pcolor 2]

;add Insulin receptors (I-R) into the membrane
  ask patches with [pcolor = 49] [
    if  pxcor = 4 or  pxcor = 14 or    ;muscle I-R
        pxcor = -17 or pxcor = -11    ;Liver I-R
    [set pcolor 123]
  ]

 ask patches with [pcolor = 123]
     [sprout-I-receptors 1
        [set color yellow - 2
        set size 2.5
        set shape "I-R"
        set bonding 0 ]
     ]

  ; add bilayer
   ask patches with [ pycor = 2 and pcolor = 49] [sprout-lipids 1 [set color 7 set shape "lipid-1" set size 1 set heading 0 set ycor 2]]
end 

to setup-glucose
  create-glucose round (Starting-Blood-sugar-level * 85 / 100)   ;liver side glucose
  [set color white
    set shape "glucose"
    set size 0.75
    set bonding 0
    set glycogen 0
    setxy -7 + random-float -16 2.5 + random-float 5]

   create-glucose round (Starting-Blood-sugar-level * 145 / 100)  ;muscle side glucose
  [set color white
    set shape "glucose"
    set size 0.75
    set bonding 0
    set glycogen 0
    setxy 23 + random-float -28 2.5 + random-float 5]

  create-glucose round (Starting-cytoplasmic-glucose * 85 / 100)
  [set color white
    set shape "glucose"
    set size 0.75
    set bonding 0
    set glycogen 0
    setxy -7 + random-float -16 1 + random-float -4
    ]

   create-glucose round (Starting-cytoplasmic-glucose * 145 / 100)
  [set color white
    set shape "glucose"
    set size 0.75
    set bonding 0
    set glycogen 0
    setxy 23 + random-float -28 1 + random-float -4
    ]


  create-glucose 400        ;set glycogen
  [set color 138
    set shape "glucose"
    set size 0.75
    set bonding 0
    set glycogen 1
    setxy (max-pxcor - 1) - random-float ((max-pxcor - 1) * 2) min-pycor + 5 + random-float 0.5]

  adjust-glucose-location
end 

to adjust-glucose-location
ask glucose with [ycor > min-pycor + 4 ]
  [if pcolor = 2 [ifelse random 2 = 0 [set xcor xcor + 1 ][set xcor xcor - 1 ]]]
end 

to setup-glut-4

  create-gluts 1
  [set shape "glut" set color 123 set size 1.25 set bonding 2 set name 1 set lock 0 set kind 4
    setxy -3 + random -2  -0.75]

   create-gluts 1
  [set shape "glut" set color 123 set size 1.25 set bonding 2 set name 1 set lock 0 set kind 4
    setxy 1 + random -2  -1.25]

  create-gluts 1
  [set shape "glut" set color 123 set size 1.25 set bonding 2 set name 1 set lock 0 set kind 4
    setxy 6 + random 2  -1]

 create-gluts 1
  [set shape "glut" set color 123 set size 1.25 set bonding 2 set name 2 set lock 0 set kind 4
    setxy 10 + random 2  -1.5]

  create-gluts 1
  [set shape "glut" set color 123 set size 1.25 set bonding 2 set name 3 set lock 0 set kind 4
    setxy 16 + random 2  -1.25]

    create-gluts 1
  [set shape "glut" set color 123 set size 1.25 set bonding 2 set name 4 set lock 0 set kind 4
    setxy 20 + random 2  -0.75]
end 

to setup-glut-2
 ask patches with [(pxcor = -22 or pxcor = -14 or pxcor = -8)  and pycor = 2 and pcolor = 49]
[if any? lipids-here
[ask lipids-here [die]
sprout-gluts 1 [set shape "glut" set color 86.5 set size 1.25 set kind 2 set heading 0 set bonding 0]
]]
end 

to setup-g-receptors
 ask patches with [pxcor = -19 and pycor = 2 and pcolor = 49]
  [if any? lipids-here
    [ask lipids-here [die]
   sprout-G-receptors 1 [set shape "g-r" set color 26 set size 3 set heading 0 set bonding 0 setxy -19 2.35]
]]
end 

to setup-glucagon
 ifelse [pcolor] of divider = 0
 [ ;no divider
 if blood-sugar  < 98
  [if not any? glucagons with [ycor > 1] [
    create-glucagons 10
    [ set bonding 0
    set shape "glucagon"
    set size 1.75
    set color 64
      setxy min-pxcor + 1 +  random 5 2.5 + random-float 5]]]


  if blood-sugar > 103
  [if count glucagons != 0
    [ask glucagons with [ycor > 0] [die]
       ]
  ]
  ]

  [;with the divide

 if blood-sugar-l  < 98
  [if not any? glucagons with [ycor > 1 and xcor <= -6] [
    create-glucagons 10
    [ set bonding 0
    set shape "glucagon"
    set size 1.75
    set color 64
      setxy min-pxcor + 1 +  random 5 2.5 + random-float 5]]]

  if blood-sugar-l > 103
  [if count glucagons with [ycor > 1 and xcor <= -6] != 0
    [ask glucagons with [ycor > 1 and xcor <= -6] [die]
        ]
  ]

     if blood-sugar-r  < 98
  [if not any? glucagons with [ycor > 1 and xcor > -6] [
    create-glucagons 10
    [ set bonding 0
    set shape "glucagon"
    set size 1.75
    set color 64
      setxy 0.5 + random 20 2.5 + random-float 5]]]

  if blood-sugar-r > 103
  [if count glucagons with [ycor > 1 and xcor > -6] != 0
    [ask glucagons with [ycor > 1 and xcor > -6] [die]]
  ]
  ]
end 

to setup-insulin

  ifelse [pcolor] of divider = 0
 ;no divider
  [
   if blood-sugar > 140 and Can-produce-insulin?
    [if not any? insulins with [ycor > 2] [
    create-insulins 20
    [ set bonding 0
    set shape "insulin"
    set size 2
    set color 95
      setxy (min-pxcor + 1) + random-float ((max-pxcor - 1) * 2) 2.5 + random-float 5]]]

  ask insulins  with [ycor > -4]
  [if pcolor = 2 [ifelse random 2 = 0 [set xcor xcor + 1 ][set xcor xcor - 1 ]]]

  if blood-sugar  < 120
  [if count insulins != 0
    [ask insulins with [ycor > 2] [die]]
  ]
  ]

  ;with the divider
  [
    ;left
  if blood-sugar-l > 140 and Can-produce-insulin?
    [if not any? insulins with [ycor > 2 and xcor <= -6] [
    create-insulins 10
    [ set bonding 0
    set shape "insulin"
    set size 2
    set color 95
    setxy -7 + random-float -16 2.5 + random-float 5]]]

  if blood-sugar-l  < 120
  [if count insulins with [ycor > 2 and xcor <= -6] != 0
    [ask insulins with [ycor > 2 and xcor <= -6] [die]]
  ]

    ;right

   if blood-sugar-r > 140 and Can-produce-insulin?
    [if not any? insulins with [ycor > 2 and xcor > -6] [
    create-insulins 10
    [ set bonding 0
    set shape "insulin"
    set size 2
    set color 95
    setxy 23 + random-float -28 2.5 + random-float 5]]]


  if blood-sugar-r  < 120
  [if count insulins with [ycor > 2 and xcor > -6] != 0
    [ask insulins with [ycor > 2 and xcor > -6] [die]]
  ]

  ]
end 

to setup-legend
 create-legends 13
  [set shape "legend"]

 ask legend 0
  [set label "lipids"
    setxy -13 -4.75 ]

  create-lipids 1
  [set color 7
    set shape "lipid-1"
    set size 0.75
    set heading 0
    setxy -13 -4.25 ]

  ask legend 1
  [set label "Glucose"
    setxy -8 -4.75]

  Create-glucose 1
  [set color white
    set shape "glucose"
    set size 1.25
    set heading 0
    set glycogen 2
    setxy -8.5 -4.25]

  ask legend 2
  [set label "Glycogen"
    setxy -2.5 -4.75 ]

  Create-glucose 2
  [set color 138
    set shape "glucose"
    set size 1.25
    set glycogen 2
    setxy -3 + random-float 0.5 -4.25]

  ask legend 3
  [set label "Glucose Transporter 4"
    setxy 14 -4.75 ]

  create-gluts 1
  [set shape "glut"
    set color 126.5
    set size 0.75
    set heading 0
    set bonding 2
    set lock 2
    setxy 12 -4.25]

 ask legend 4
  [set label "Insulin"
    setxy -7.8 -7.25 ]

 create-insulins 1
  [ set bonding 0
    set shape "insulin"
    set size 1.25
    set color 95
    setxy -8 -6.75]

  ask legend 5
  [set label "Insulin"
    setxy  -2.8 -7.15 ]

ask legend 6
  [set label "Receptor"
    setxy  -2.5 -7.65 ]

  create-I-receptors 1
       [set color yellow
        set size 0.75
        set shape "I-R"
        setxy -3 -6.5]


   ask legend 7
  [ set label "Glucose Transporter 2"
    setxy 7 -4.75 ]

  create-gluts 1
  [set shape "glut"
    set color 86.5
    set size 0.75
    set heading 0
    set bonding 2
    setxy 5 -4.25]

ask legend 8
  [set label "Glucagon"
    setxy  2.75 -7.25 ]

create-Glucagons 1
  [set color 64
    set shape "Glucagon"
    set size 1.25
    set heading 90
    setxy 2.25 -6.75
  ]

 ask legend 9
  [set label "Glucagon"
    setxy  8.5 -7.15 ]

ask legend 10
  [set label "Receptor"
    setxy  8.5 -7.65 ]

create-G-receptors 1
  [set color 26
    set shape "g-r"
    set size 0.75
    set heading 90
    setxy 8 -6.5
  ]

  ask legend 11
  [set label "LIVER"
    setxy  -20.5 -3.5 ]

  ask legend 12
  [set label "MUSCLE"
    setxy  21 -3.5 ]

  create-lipids 1
  [set color 7
    set shape "line"
    set size 26
    set heading 90
    setxy 0 -5.75
  ]
end 

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;;                                                                           ;;
;;         Sub-procedures of GO                                              ;;
;;                                                                           ;;
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to glucose-movement
  ask glucose with [glycogen = 0] [
  ifelse bonding = 0
  [ if pcolor = 0
      [right random 90 left random 90   ;wiggle
         if [pcolor] of patch-at dx dy = 0 [fd 0.2]   ;If nothing is ahead, move forward
    ]
    if any? gluts-on patch-ahead 1 [
      let my-channel one-of gluts-on patch-ahead 1
      if [bonding] of my-channel = 0 [
       set color red move-to my-channel set bonding 1

          ask my-channel [set bonding 1 ifelse kind = 2 [set color 85][set color 127.5]]]]]
  [ifelse xcor <= -6
    [ifelse blood-sugar-l > cyto-glucose-l
      [set heading 180 fd 0.1] [set heading 0 fd 0.1]
        if pcolor = 0 [set bonding 0 set color white]]
      [ifelse blood-sugar-r > cyto-glucose-r
      [set heading 180 fd 0.2] [set heading 0 fd 0.2]
        if pcolor = 0 [set bonding 0 set color white]]
        ]
  ]

  ask gluts with [bonding = 1] [if count glucose-here = 0 [set bonding 0 ifelse kind = 2 [set color 86.5][set color 126.5]]]
end 

to check-glucose-location ;detemine glucose location
  ask glucose [ifelse ycor > 2 [set cyto 0][set cyto 1]]
end 

to insulin-movement
  ask insulins with [ycor > 2]
  [if bonding = 0
    [
      if pcolor = 0
      [right random 90 left random 90   ;wiggle
         if [pcolor] of patch-at dx dy = 0 [fd 0.2]
      ]

      if any? I-receptors in-radius 3 with [bonding = 0] [
      let my-receptor one-of I-receptors in-radius 3 with [bonding = 0]
        set heading 0 move-to my-receptor set ycor ycor + 1.2  set bonding 1

        ask my-receptor [set bonding 1 set color yellow]]]
      ]

 ifelse [pcolor] of divider = 0
  [;no divide
  ask I-receptors with [bonding = 1]
    [if count insulins with [ycor > 2] = 0 [set bonding 0 set color yellow - 2]]]
  [;with the divide
    ask I-receptors with [bonding = 1 and xcor <= -6]
    [if count insulins with [ycor > 2 and xcor <= -6] = 0 [set bonding 0 set color yellow - 2]]

    ask I-receptors with [bonding = 1 and xcor > -6]
    [if count insulins with [ycor > 2 and xcor > -6] = 0 [set bonding 0 set color yellow - 2]]
  ]
end 

to glut-4-movement

  ifelse count I-receptors with [bonding = 1 and xcor > -6 ] > 0 or exercise?
    [ask gluts with [kind = 4 and lock = 0]
      [glut-recruiting]]

    [ask gluts with [kind = 4 and lock = 1]
      [glut-restore]]
end 

to glut-recruiting

  let loci  min-one-of lipids with [pycor = 2] [distance myself]
 face loci
 ifelse (distancexy [xcor] of loci [ycor] of loci) > 0.3
  [ifelse pcolor = 9 [rt random 90 lt random 90][fd 0.1]]
 [move-to loci set heading 0 set lock 1 set bonding 0 set color 126.5
  ask lipids-here [die] ]
end 

to glut-restore
  set bonding 2
  if pcolor = 49 [set heading 180 fd 0.25]
  if pcolor = 0 [ifelse pcolor = 2 [ifelse pxcor > 10 [set heading -90 fd 0.5][set heading 90 fd 0.5]][rt random 15 lt random 15 fd 0.1 set color 123]]
  if pycor < -0.75 [if random 100 < 25 [set lock 0]]
end 

to glucagon-movement
  ifelse [pcolor] of divider = 0
  [;no divide

  ask glucagons with [ycor > 2]
  [if bonding = 0
    [
      if pcolor = 0
      [right random 90 left random 90   ;wiggle
         if [pcolor] of patch-at dx dy = 0 [fd 0.2]
      ]

      if any? G-receptors in-radius 2 with [bonding = 0] [
      let my-receptor one-of G-receptors in-radius 2 with [bonding = 0]
        set heading 0 move-to my-receptor set xcor xcor - 0.3 set ycor ycor + 0.95 set bonding 1

        ask my-receptor [set bonding 1 set color 27]]]
      ]

  ask G-receptors with
    [bonding = 1] [if count glucagons with [ycor > 2] = 0 [set bonding 0 set color 26]]
  ]

  [;with the divide

    ask glucagons with [ycor > 2]
  [if bonding = 0
    [
      if pcolor = 0
      [right random 90 left random 90   ;wiggle
         if [pcolor] of patch-at dx dy = 0 [fd 0.2]
      ]

      if any? G-receptors in-radius 2 with [bonding = 0] [
      let my-receptor one-of G-receptors in-radius 2 with [bonding = 0]
        set heading 0 move-to my-receptor set xcor xcor - 0.3 set ycor ycor + 0.95 set bonding 1

        ask my-receptor [set bonding 1 set color 27]]]
      ]

  ask G-receptors with
    [bonding = 1] [if count glucagons with [ycor > 2 and xcor <= -6] = 0 [set bonding 0 set color 26]]

  ]
end 

to glycolysis

   ifelse [pcolor] of divider = 0
  [;no divider
  ask glucose with [glycogen = 0 and cyto = 1] [
  if random 100 < (20 + (count insulins with [bonding = 1])* 20)
   [ if random 100000 < metabolic-rate  [die]
  ]]]

  [;with the divider
    ask glucose with [glycogen = 0 and xcor <= -6 and cyto = 1] [
  if random 100 < (20 + (count insulins with [bonding = 1 and xcor <= -6])* 35)
      [ if random 100000 < metabolic-rate  [die]]]

    ask glucose with [glycogen = 0 and xcor > -6 and cyto = 1] [
  if random 100 < (20 + (count insulins with [bonding = 1 and xcor > -6])* 35)
      [ if random 100000 < metabolic-rate  [die]]]
  ]
end 

to glycogenesis-glycogenolysis

  ;left
    if glycogen-level-l = 0
   [if count glucose with [cyto = 1 and xcor <= -6] != nobody
     [ask one-of glucose with [cyto = 1 and xcor <= -6]    ;set a starter
        [set glycogen 1
         set color 138
         setxy (min-pxcor + 1) + random-float 10 -2 + random-float -1 ]]]

  if cyto-glucose-l > 80 and glycogen-level-l < 800 [
    ask glucose with [cyto = 1 and glycogen = 0 and xcor <= -6 ]      ;glycogenesis
     [if any? other glucose-here with [glycogen = 1]
      [if random 100 < (1 + (count insulins with [bonding = 1])* 45)
        [ set glycogen 1 set color 138]
  ]]]


   if any? G-receptors with [bonding = 1]                ;glycogenolysis
    [ask glucose with [cyto = 1 and glycogen = 1 and xcor <= -6]
     [if random 1000 < 5
      [set glycogen 0 set color white
       set heading 45 - random 90
          fd 0.5]]
    ]


     ;right

   if glycogen-level-r = 0
   [if count glucose with [cyto = 1 and xcor > -6] != nobody
     [ask one-of glucose with [cyto = 1 and xcor > -6]    ;set a starter
        [set glycogen 1
         set color 138
         setxy 1 + random-float 20 -2 + random-float -1 ]]]

    if cyto-glucose-r > 80 and glycogen-level-r < 400 [
    ask glucose with [cyto = 1 and glycogen = 0 and xcor > -6 ]      ;glycogenesis
     [if any? other glucose-here with [glycogen = 1]
      [if random 100 < (1 + (count insulins with [bonding = 1])* 45)
        [ set glycogen 1 set color 138]
  ]]]

   if cyto-glucose-r <= 80               ;glycogenolysis
    [ask glucose with [cyto = 1 and glycogen = 1 and xcor > -6]
     [if random 1000 < 5
      [set glycogen 0 set color white
       set heading 45 - random 90
          fd 0.5]]
    ]
end 

to recover-lipids
  ask patches with [pcolor = 49]
  [if not any? turtles-here [sprout-lipids 1[set color 7 set shape "lipid-1" set size 1 set heading 0 set ycor 2]]]
end 

to set-insulin-sensitivity
  ask I-receptors with [ycor > 0]
    [ifelse Insulin-resistance?
      [set bonding 2 set color yellow - 2]
      [ifelse color = yellow [set bonding 1][set bonding 0]]
      ]
end 

to divide
  ask divider [ifelse pcolor = 2 [set pcolor 0] [set pcolor 2]]
end 

to food-intake
  set clock clock + 1
  if clock = 1200 [
    if eat-every-4-hrs?
  [
  create-glucose round (100 * 85 / 100)   ;add 100 liver side glucose
  [set color white
    set shape "glucose"
    set size 0.75
    set bonding 0
    set glycogen 0
    setxy -7 + random-float -16 2.5 + random-float 5]

  create-glucose round (100 * 145 / 100)  ;muscle side glucose
  [set color white
    set shape "glucose"
    set size 0.75
    set bonding 0
    set glycogen 0
    setxy 23 + random-float -28 2.5 + random-float 5]

 ask glucose with [ycor > -4]
  [if pcolor = 2 [ifelse random 2 = 0 [set xcor xcor + 1 ][set xcor xcor - 1 ]]]
  ]
    set clock 0]
end 

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;;                                                                           ;;
;;         Supporting-procedures                                             ;;
;;                                                                           ;;
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;

to plot-levels ;; this creates creates the bar graph
    set-current-plot "Glucose Gradient"
    clear-plot
    plot-pen-down
    set-current-plot-pen "Blood sugar (Liver)"
    plotxy 1 blood-sugar-l
    set-current-plot-pen "Cytoplasmic glucose (Liver)"
    plotxy 2 cyto-glucose-l
    set-current-plot-pen "Blood sugar (Muscle)"
    plotxy 4 blood-sugar-r
    set-current-plot-pen "Cytoplasmic glucose (Muscle)"
    plotxy 5 cyto-glucose-r
end 


; Copyright 2021 by Lin Xiang.  All rights reserved.