Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate...
-
Upload
michael-ferguson -
Category
Documents
-
view
213 -
download
0
Transcript of Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate...
![Page 1: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/1.jpg)
Lecture 8
Glucose Disposal
![Page 2: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/2.jpg)
Post-Prandial Glucose Rise
• Blood glucose goes up after a carbohydrate meal– Uptake and disposal mediated by insulin
• Glucose challenge– 1 g/kg body weight, or 50 g or 70 g– Measure blood glucose changes
• “Normal” is 5 mM at time zero• rises to a peak at about 30 min• back down to basal by 60 min
– Glucose intolerance• glucose peak is higher and time to return to basal is longer• Glucose is not being taken up properly
![Page 3: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/3.jpg)
Glucose responses
BloodGlucose(mM)
5
10
Time (h)
0 1 2
Intolerant
Tolerant
![Page 4: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/4.jpg)
Consequences of Intolerance
• Post-prandial hyperglycemia is a problem– If occurs after each meal and persists for several
hours then there will be problems• The person will rarely be euglycemic!• Leads to complications of hyperglycemia
– Root cause may be insulin resistance• Impaired ability of tissues to respond to insulin• Underlies Type II Diabetes
• Control of glucose intolerance– Insulin injections– Consumption of slowly absorbed starches
![Page 5: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/5.jpg)
Starch Digestion
BloodGlucose(mM)
5
10
Time (h)
0 1 2
Amylose
Amylopectin
Different Glycemic Responses
![Page 6: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/6.jpg)
The Glycemic Index
• Describes the post-prandial glucose response– Area under the ‘test’ food glucose curve divided by– Area under a ‘reference’ food glucose curve
• Reference food is normally 50 g gluocse• Test food given in an amount that will give 50 g digestible
carbohydrate– Expressed as a %– GI of modern, processed, amylopectin foods >80– GI of legumes < 30
• Useful knowledge for controlling blood glucose – Especial relevance to diabetes– QUALITY of carbohydrate (GI) as important as total
amount of carbohydrate
![Page 7: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/7.jpg)
GI critics say..• Area under slowly absorbed may be the same as quickly
absorbed– Look closely at previous figure
• The GI should not apply to foods other than starches– Sugary foods are low GI
• Because half the carbohydrate is fructose• Similarly, fructose containing foods are low GI
– Dairy foods are low GI• Because half the carbohydrate is galactose
• Claims of “slow burning energy” debatable– What regulates energy expenditure and what determines ‘supply’
of substrates– Even if supply was important, the classic “persistently but subtly”
raised post-prandial glucose response is hardly ever seen• Some Low GI values may be more related to inaccurate
estimation of digestible carbohydrate portions
![Page 8: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/8.jpg)
Glucose Disposalglucose
glucose G6P
Glycogen
F16BP
pyruvate
pyruvate acetyl-CoA
acetyl-CoA
Fatty Acids
CO2
GLUTs
GLYCOGENESIS
GLYCOLYSIS
KREBS CYCLE
LIPOGENESIS
Fat
![Page 9: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/9.jpg)
Glucose Transporters
• GLUT-1– Present in all cells at all times in constant amounts– Catalyze basal transport
• GLUT-4– Insulin dependent– Present in muscle and WAT only– Translocation and fusion – in response to insulin, vesicles
that contain GLUT-4 move from Golgi Apparatus and fuse with cell membrane
– Translocation is stimulated when insulin binds to its receptor or in response to exercise
![Page 10: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/10.jpg)
glucose
glucose G6P
GLUTs GLYCOGENESIS
GLYCOLYSIS
glucose
insulin
Translocation
Vesicles in Golgi
PFK – phosphofructo kinase
GS – glycogen synthase
Muscle Glucose Uptake
![Page 11: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/11.jpg)
Rate Limiting Enzymes• The slowest enzyme in the metabolic pathway determines the
overall speed – Rate-limiting step – Flux generating step
• Properties of these enzymes– Irreversible
• Need alternative enzymes to ‘go back’• Not ‘equilibrium’ under physiological conditions• Committed steps
– Saturated with substrate• Low Km or [S] >> Km• Working at Vmax
• Key points of regulation
![Page 12: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/12.jpg)
Enzyme kinetics
• At high [substrate], minor changes in [substrate] will not affect the rate of reaction
• Doubling or halving the [S] isn’t even going to affect the rate
[substrate]
Rate
Vmax
½ Vmax
Km S1 S2
![Page 13: Lecture 8 Glucose Disposal. Post-Prandial Glucose Rise Blood glucose goes up after a carbohydrate meal –Uptake and disposal mediated by insulin Glucose.](https://reader038.fdocuments.us/reader038/viewer/2022110210/56649e625503460f94b5e22b/html5/thumbnails/13.jpg)
Redfern Station Analogy• Imagine a railway station at peak hour with just one barrier operating
– This step will soon become ‘saturated’ with people– It is the ‘rate limiting’ step– The point of regulation of the rate of the people moving pathway!
• There are 3 major ways to regulate this (and metabolic!) pathways– Change the intrinsic activity of the step
• Make ticket-reading & gate-opening happen faster• Akin to Allostery
– molecules bind to allosteric site of an enzyme and influence the activity of the active site
– Make more gates open• Switch them from being ‘off’ to ‘on’• Or change the direction from ‘in’ to out• Akin to Covalent Modification and reversible phosphorylation
– transporters working more activated enzymes
– Make and destroy gates according to need • Akin to making more enzymes (and then degrading them later!)• This very energy consuming and seemingly inefficient, involving
– Transcription of genes– Translation of mRNA