Benjamin Bikman, PhD Associate Professor Brigham Young University. Insulin vs. Glucagon. The relevance of dietary protein

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1 Benjamin Bikman, PhD Associate Professor Brigham Young University nsulin vs. lucagon The relevance of dietary protein

2 nsulinq.com BestFats.com

3 Update Final update next year

4 Anabolism Feeding and Storing nsulin β α lucagon Catabolism Fasting and Burning

5 Anabolism Feeding and Storing Catabolism Fasting and Burning lycogenesis Protein synthesis Nothing Lipogenesis Lipolysis* Lipogenesis lycogenesis lycogenolysis luconeogenesis Lipolysis Ketogenesis Deeber et al FEBS Letters Liljenquist et al JC

6 Anabolism Feeding and Storing Catabolism Fasting and Burning lycogenesis Protein synthesis Nothing Lipogenesis Lipolysis* Lipogenesis lycogenesis lycogenolysis luconeogenesis Lipolysis Ketogenesis Deeber et al FEBS Letters Liljenquist et al JC

7 Carb Protein Fat

8 Carb Protein Fat One of these depends on context Shalch et al JC Bottger et al.1973 JC

9 Carb Protein Fat One of these depends on context Depends on glycemia Shalch et al JC Bottger et al.1973 JC

10 Carb Protein Fat Alanine is the prototypical gluconeogenic amino acid lucose infusion (hyperglycemia) Followed by alanine infusion Significant increase in insulin (~130 uu) Significant decrease in glucagon (~45 pg) Fasted (euglycemia) Followed by alanine infusion No significant increase in insulin (~6 uu) Significant increase in glucagon (~100 pg)

11 Carb Protein Fat Lipogenesis lycogenesis lycogenolysis luconeogenesis Lipolysis Ketogenesis Can t afford to inhibit gluconeogensis Fasted (euglycemia) Followed by alanine infusion No significant increase in insulin (~6 uu) Significant increase in glucagon (~100 pg)

12 Carb Protein Fat Shalch et al JC Bottger et al.1973 JC

13 Carb Protein Fat nsufficient stimulus? Anabolic Anabolic No effect Anabolic Anabolic/Catabolic Catabolic Anabolic Anabolic/Catabolic Catabolic Shalch et al JC Bottger et al.1973 JC

14 Carb Protein Fat nsufficient stimulus? Anabolic Anabolic Anabolic Anabolic/Catabolic Anabolic Anabolic/Catabolic A helpful No effect way to appreciate Catabolicthe relevance Catabolic is to know the nsulin:lucagon ratio Shalch et al JC Bottger et al.1973 JC

15 The insulin:glucagon ratio is an indicator of the predominating metabolic function High Anabolism Feeding and Storing Low Catabolism Fasting and Burning A helpful way to appreciate the relevance is to know the nsulin:lucagon ratio

16 The Relevance of a low : without calorie restriction grantome.com/grant/nh/k08-dk A low : elicits the benefits of a fasted state 1.nsulin sensitivity 2.Autophagy a. Mitophagy 3.Lipolysis 4.BAT activation

17 S.A.D. Fasting Low-carb

18 ~.8 Fasting Catabolic lycogenolysis luconeogenesis Lipolysis Ketogenesis

19 ~4 Anabolic S.A.D. lycogenesis Lipogenesis nhibition of: Autophagy Ketogenesis

20 ~1.3 Low-carb Catabolic lycogenolysis luconeogenesis Lipolysis Ketogenesis

21 S.A.D. Fasting Protein Low-carb

22 ~.8 Fasting Protein ~.5

23 ~70 S.A.D. Protein ~4

24 ~1.3 Low-carb Protein ~1.3

25 Protein 1g/kg ~4 ~70 ~1.3 ~1.3 S.A.D. Low-carb

26 Without exception, the insulin:glucagon ratio declines as need for endogenous glucose production and/or fuel production increases. Roger Unger, 1971

27 The need for the liver to create glucose determines the : response to protein nhibits gluconeogenesis Activates gluconeogenesis Who actually needs glucose? No need S.A.D. Low-carb High need luconeogenesis

28 But what else do insulin and glucagon regulate at the liver? Protein s the potential increase in insulin sufficient to inhibit ketogenesis? S.A.D. Low-carb Ketogenesis

29 Ketogenesis How are ketones made? Low insulin is one part ncreased glucagon is another part

30 Ketogenesis How are ketones made? Low insulin is one part ncreased glucagon is another part Low insulin does little to ketogenesis in the absence of increased glucagon lucagon No lucagon lucagon No lucagon Endocrinology, Volume 158, ssue 4, 1 April 2017, Pages nsulin No nsulin

Ketogenesis How are ketones made? Low insulin is one part lucagon appears to be the primary hormone in the induction of ketogenesis in the liver.

31 Ketogenesis How are ketones made? Low insulin is one part lucagon appears to be the primary hormone in the induction of ketogenesis in the liver. Denis Mcarry, 1982 ncreased glucagon is another part Low insulin does little to ketogenesis in the absence of increased glucagon Endocrinology, Volume 158, ssue 4, 1 April 2017, Pages lucagon nsulin No lucagon lucagon No lucagon No nsulin But it s more than just hormones

32 Ketogenesis How are ketones made? Carnitine Escorts fat into the mitochondria for oxidation

33 Ketogenesis How are ketones made? Carnitine Escorts fat into the mitochondria for oxidation Ketogenesis doubles with addition of carnitine

34 Ketogenesis How are ketones made? Carnitine + + = Ketones

35 Ketogenesis How are ketones made? Protein + + = Ketones Fat Carnitine

36 Both emphasize a reduced consumption of carbohydrates Fat Protein Carb Vs. Fat Protein Carb Underlying glycemic state may be useful for determining which is best

37 Euglycemia Euinsulinemia With improved glycemia and insulin Hyperglycemia Hyperinsulinemia Fat Protein Carb Vs. Fat Protein Carb Underlying glycemic state may be useful for determining which is best

38 Euglycemia Euinsulinemia With improved glycemia and insulin Hyperglycemia Hyperinsulinemia Fat Protein Carb Vs. Fat Protein Carb Once glucose and insulin are controlled, a shift may be helpful

39 How To Maintain a Low : Protein Carb Fat 3. Fill with Fat 2. Prioritize Protein 1. Control Carbohydrates

40 How To Maintain a Low : Vs. ood Little insulin effect Not so ood Large insulin effect 1. Control Carbohydrates < 50 g/day

41 How To Maintain a Low : Age 1-2 g/kg BW/day 2. Prioritize Protein bjsm.bmj.com/content/early/2018/01/18/bjsports

42 How To Maintain a Low : ood Vs. Not so ood Constitutes all remaining caloric needs 3. Fill with Fat

43 How To Maintain a Low : 3. Fill with Fat 2. Prioritize Protein 1. Control Carbohydrates

44 Facebook: Benjamin T. Bikman

Energy metabolism - the overview

Energy metabolism - the overview Josef Fontana EC - 40 Overview of the lecture Important terms of the energy metabolism The overview of the energy metabolism The main pathways of the energy metabolism