Banting renumbered

1
Genetic Predisposition
Environmental Factors
Obesity
Hyperinsulinemia with Normal Glucose Tolerance
Impaired Glucose Tolerance
65 ?-cell defect
Figure A1.
2
Minimal Model
Glucose levels
Insulin sensitivity (SI)
?-cell response
Insulin levels
Insulin injection
Glucose injection
Figure A2.
3
Figure A3.
4
2500
Week 0
2000
Week 2
Week 4
1500
Week 6
Secretion
1000
500
0
0
1
2
3
4
5
6
7
8
Insulin Sensitivity
Figure A4.
5
Figure A4
Figure A5
Cause of Hyperinsulinemia? Conventional wisdom
Increased fasting glycemia and/or impaired
glucose tolerance
Hyperinsulinemia (Increased secretion, Reduced
clearance)
Figure A5.
6
6 WKS FAT FEEDING
BASELINE
9.0
300

Insulin


6.0
200
pM
pM


3.0
100
GLP-1


0
0.0
125
4.0
Glucose
ng/mL
mg/dL
100

2.0
GH
75
0.0
8.0

1.0


FFA







Cortisol

6.0
0.8



0.6
µg/mL
4.0
mM

0.4
2.0
0.2
0.0
0.0
6am
9
12pm
3
6pm
9
12am
3
6am
6am
9
12pm
3
6pm
9
12am
3
6am
Figure A6.
7
INSULIN IN PLASMA AND INTERSTITIAL FLUID
Hand-in-glove relationship between interstitial
insulin and glucose disposal
Figure A7.
8
Figure A8.
9
Figure A9.
10
Figure A10.
11
Transendothelial transport barrier
Insulin
FFA
adipocytes
GLUCOSE PRODUCTION
Figure A11.
12
Week 0
Week 6
35






Dog 1
30
Body Weight (kg)
25
Dog 2
20
-2
0
2
4
6
Weeks on diet
1000
Dog 3

750
110
Body Fat (cm3)

500
Omental
Dog 4
115
250
SubQ
0
Figure A12.
Week 0
Week 6
13
Resistant Liver
Visceral Fat
FFA
Figure A13.
14
ß3-blockade
0.4
0.3
0.2
0.1
0.4
Free Fatty Acids
0.3
0.2
0.1
0.4
0.3
0.2
0.1
Figure A14.
15
Pulsatile Lipolysis
FFA
Constitutive Lipolysis
GH TSH, PTH ANP Glucocorticoids intrinsic
Figure A15.