Blood sugar regulation by the liver

;;
;; This model is developed by Dr. Lin Xiang at the University of Kentucky. Contact: lin.xiang@uky.edu
;;
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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]
glucose-own [bonding cyto glycogen]
I-receptors-own [bonding]
G-receptors-own [bonding]
glucagons-own [bonding]

globals[clock]

to-report blood-sugar
  report count glucose with [ycor > 2 and color = white and bonding = 0]
end 

to-report cyto-glucose
  report count glucose with [ycor < 2 and color = white and bonding = 0 and glycogen = 0]
end 

to-report glycogen-level
  report count glucose with [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
 setup-g-receptors
 set-insulin-sensitivity

reset-ticks
end 

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


check-glucose-location
food-intake
set-insulin-sensitivity
setup-insulin
setup-glucagon
glucose-movement
insulin-movement
glucagon-movement
glycolysis
glycogenesis-glycogenolysis
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]

;add Insulin receptors (I-R) into the membrane
  ask patches with [pcolor = 49] [
    if  pxcor = -2 or
        pxcor = 6
    [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 Starting-Blood-sugar-level
  [set color white
    set shape "glucose"
    set size 0.75
    set bonding 0
    set glycogen 0
    setxy (max-pxcor - 1) - random-float ((max-pxcor - 1) * 2) 2.5 + random-float 5]

  create-glucose Starting-cytoplasmic-glucose
  [set color white
    set shape "glucose"
    set size 0.75
    set bonding 0
    set glycogen 0
    setxy (max-pxcor - 1) - random-float ((max-pxcor - 1) * 2) 1 + random-float -4]

  create-glucose 200        ;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]
end 

to setup-glut
 ask patches with [(pxcor = 2 or pxcor = -10 or pxcor = 10)  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 heading 0 set bonding 0]
]]
end 

to setup-insulin

 if blood-sugar > 140 and can-produce-insulin?     ;only produce insulin when blood sugar level is high and capable of producing insulin
  [if not any? insulins with [ycor > 2] [
    create-insulins 10
    [ set bonding 0
    set shape "insulin"
    set size 2
    set color 95
      setxy -6 + random-float 16 2.5 + random-float 5]]]

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

to setup-g-receptors
 ask patches with [pxcor = -6 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 -6 2.35]
]]
end 

to setup-glucagon

 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 -10 + random 5 2.5 + random-float 5]]]

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

to setup-legend
 create-legends 10
  [set shape "legend"]

 ask legend 0
  [set label "lipids"
    setxy -8 -4.75 ]

  create-lipids 1
  [set color 7
    set shape "lipid-1"
    set size 0.75
    set heading 0
    setxy -8 -4.25 ]

  ask legend 1
  [set label "Glucose"
    setxy -2.75 -4.75]

  Create-glucose 1
  [set color white
    set shape "glucose"
    set size 1.25
    set heading 0
    set glycogen 2
    setxy -3 -4.25]

  ask legend 2
  [set label "Glycogen"
    setxy 2.75 -4.75 ]

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

  ask legend 3
  [ set label "Glucose Transporter 2"
    setxy 10 -4.75 ]

  create-gluts 1
  [set shape "glut"
    set color 86.5
    set size 0.75
    set heading 0
    set bonding 2
    setxy 8 -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 -6.75]

ask legend 7
  [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 8
  [set label "Glucagon"
    setxy  8.5 -7.15 ]

ask legend 9
  [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 -6.75
  ]

  create-lipids 1
  [set color 7
    set shape "line"
    set size 22
    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 set color 85]]]]
  [
    ifelse blood-sugar > cyto-glucose
      [set heading 180 fd 0.1] [set heading 0 fd 0.1]
      if pcolor = 0 [set bonding 0 set color white]
        ]
  ]

  ask gluts with [bonding = 1] [if count glucose-here = 0 [set bonding 0 set color 86.5]]
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 2 with [bonding = 0] [
      let my-receptor one-of I-receptors in-radius 2 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]]]
      ]

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

to glucagon-movement
  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]]
end 

to glycolysis
  ask glucose with [glycogen = 0 and cyto = 1] [
    if random 1000000 < metabolic-rate  [die]
  ]
end 

to glycogenesis-glycogenolysis

  if glycogen-level = 0
   [if count glucose with [cyto = 1] != nobody
     [ask one-of glucose with [cyto = 1]    ;set a starter
        [set glycogen 1
         set color 138
         setxy (max-pxcor - 1) - random-float ((max-pxcor - 1) * 2) -2 + random-float -1 ]]]

  if glycogen-level < 800 [       ;glycogenesis set a max glycogen
  ask glucose with [cyto = 1 and glycogen = 0]
     [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]
     [if random 1000 < 5
      [set glycogen 0 set color white
       set heading 45 - random 90
          fd 0.5]]
    ]
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 food-intake
  set clock clock + 1
  if clock = 1200 [
    if eat-every-4-hrs?
  [create-glucose 100
  [set color white
    set shape "glucose"
    set size 1
    set bonding 0
    set glycogen 0
    setxy (max-pxcor - 1) - random-float ((max-pxcor - 1) * 2) 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                                             ;;
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to plot-levels ;; this creates creates the bar graph
    set-current-plot "Glucose Gradient"
    clear-plot
    plot-pen-down
    set-current-plot-pen "Blood stream glucose"
    plotxy 1 blood-sugar
    set-current-plot-pen "Cytoplasm glucose"
    plotxy 2 cyto-glucose
    set-current-plot-pen "Glycogen"
    plotxy 3 glycogen-level
end